Do birds select the plastics debris used for nest construction? A case study in a Mediterranean agricultural landscape.

Plastic pollution is becoming a global problem due to its ubiquitous occurrence and the impacts detected for many species. However, the research about plastics in nests of terrestrial bird species has remained relatively overlooked in comparison to those devoted to marine ecosystems. Here we study the occurrence and patterns of use of anthropogenic material in nests of two passerine birds, the Eurasian magpie (Pica pica) and the European serin (Serinus serinus), breeding in an orange tree cultivation in Mediterranean Spain. Our results show that both species use extensively plastic debris as nest material; almost 71% of the European serin nests and 96% of nests of Eurasian magpies contained plastic debris. Furthermore, by analyzing the plastic debris availability in the agricultural landscape surveyed we confirmed a selection pattern in the two species. Thus, both species preferably select plastic filaments over other plastic debris. The Eurasian magpie does not select plastic based on size or color but the European serin avoid black plastics prefer smaller fragments in comparison to the average size available. Moreover, we suggest the apparent similarity of plastic filaments with the natural materials typically used by these species, as well as how they use the plastic in their nests could influence their selection behavior. More studies focused on terrestrial birds inhabiting human modified habitats could offer a deeper approach to how plastic debris interacts with wildlife in different ways.

X-ray imageable, drug-loaded hydrogel that forms at body temperature for image-guided, needle- based locoregional drug delivery.

Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution. Thus, drug delivery varies widely, highly-dependent upon technique. An x-ray imageable poloxamer 407 (POL)-based drug delivery gel was developed and characterized, enabling real-time feedback. Utilizing three needle devices, POL or a control iodinated contrast solution were injected into an ex vivo bovine liver. The 3D distribution was assessed with cone beam computed tomography (CBCT). The 3D distribution of POL gels demonstrated localized spherical morphologies regardless of the injection rate. In addition, the gel 3D conformal distribution could be intentionally altered, depending on the injection technique. When doxorubicin (DOX) was loaded into the POL and injected, DOX distribution on optical imaging matched iodine distribution on CBCT suggesting spatial alignment of DOX and iodine localization in tissue. The controllability and localized deposition of this formulation may ultimately reduce the dependence on operator technique, reduce systemic side effects, and facilitate reproducibility across treatments, through more predictable standardized delivery.

Difficulties of gender affirming treatment in trans women with BRCA1+ mutation: A case report.

Gender affirming treatment in transgender women is based on a combination of antiandrogens and estrogens, with the latter maintained over the long term. When prescribing these treatments, we must consider the possibility of developing estrogen-dependent breast cancer. In transgender women, a breast cancer incidence of 4.1 per 100,000 has been estimated, which would increase the risk by 46% in relation to cisgender men but decrease it by 70% in relation to cisgender women. It is known that certain gene mutations such as BRCA1 imply an increased risk of breast cancer, but at present the risk in transgender women with BRCA1 treated with estrogens is not well established. We present the case of a transgender woman with a family history of breast cancer and BRCA1 mutation and the therapeutic decisions made in a multidisciplinary team. Following this case, we review and discuss the published literature.

Postsurgical Outcomes of Mesial Temporal Lobe Epilepsy due to Hippocampal Sclerosis Associated with Calcified Neurocysticercosis.

The aim of this study was to analyze postsurgical outcomes for individuals with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) who underwent anterior temporal lobectomy, based on the presence of calcified neurocysticercosis (cNCC). A retrospective cross-sectional study was conducted on 89 patients with MTLE-HS who underwent anterior temporal lobectomy between January 2012 and December 2020 at a basic epilepsy surgery center located in Lima, Peru. We collected sociodemographic, clinical, and diagnostic information. The postsurgical results were analyzed using bivariate analysis according to the Engel classification. We included 89 individuals with a median age of 28 years (interquartile range [IQR]: 24-37), and more than half (55.1%) were male. Seventeen (19.1%) were diagnosed with cNCC. A greater number of patients with cNCC had lived in rural areas of Peru during their early life compared with those without cNCC (12 [70.6%] versus 26 [36.1%]; P = 0.010). Patients with cNCC exhibited a greater median frequency of focal to bilateral tonic-clonic seizures per month (1 [IQR: 0-2] versus 0 [0-0.5]; P = 0.009). Conversely, a lower proportion of patients with cNCC reported a history of an initial precipitating injury in comparison to the group without cNCC (4 [23.5%] versus 42 [58.3%]; P = 0.014). At the 1-year follow-up, most patients (82.4%) with cNCC were categorized as Engel IA. Similarly, at the 2-year follow-up, nine (75.0%) were classified as Engel IA. Our findings suggest that most patients diagnosed with cNCC exhibit favorable postsurgical outcomes, comparable to those without cNCC. Additionally, it can be postulated that cNCC may play a role as an initial precipitating injury.

An unexpected journey for BNIP3.

Mitophagy is a cellular process that enables the selective degradation of damaged, dysfunctional, or superfluous mitochondria. During mitophagy, specific proteins recognize and tag mitochondria for degradation. These tagged mitochondria are engulfed by specialized structures called phagophores that then mature into autophagosomes/mitophagosomes. Mitophagosomes subsequently transport their mitochondrial cargo to lysosomes, where the mitochondria are broken down and recycled. While the PINK1-PRKN-dependent mitophagy pathway is well understood, mitophagy can also occur independently of this pathway. BNIP3 and BNIP3L/NIX, paralogous membrane proteins on the outer mitochondrial membrane (OMM), serve as ubiquitin-independent mitophagy receptors. Historically, BNIP3 regulation was thought to be primarily transcriptional through HIF1A (hypoxia inducible factor 1 subunit alpha). However, recent work has revealed a significant post-translational dimension, highlighting the strong role of the ubiquitin-proteasome system (UPS) in BNIP3 regulation. With these emerging concepts in mind, we aimed to develop a unified understanding of how steady-state levels of BNIP3 are established and maintained and how this regulation governs underlying cell physiology.

Feasibility study of a SiPM-fiber detector for non-invasive measurement of arterial input function for preclinical and clinical positron emission tomography.

Pharmacokinetic positron emission tomography (PET) studies rely on the measurement of the arterial input function (AIF), which represents the time-activity curve of the radiotracer concentration in the blood plasma. Traditionally, obtaining the AIF requires invasive procedures, such as arterial catheterization, which can be challenging, time-consuming, and associated with potential risks. Therefore, the development of non-invasive techniques for AIF measurement is highly desirable. This study presents a detector for the non-invasive measurement of the AIF in PET studies. The detector is based on the combination of scintillation fibers and silicon photomultipliers (SiPMs) which leads to a very compact and rugged device. The feasibility of the detector was assessed through Monte Carlo simulations conducted on mouse tail and human wrist anatomies studying relevant parameters such as energy spectrum, detector efficiency and minimum detectable activity (MDA). The simulations involved the use of 18F and 68Ga isotopes, which exhibit significantly different positron ranges. In addition, several prototypes were built in order to study the different components of the detector including the scintillation fiber, the coating of the fiber, the SiPMs, and the operating configuration. Finally, the simulations were compared with experimental measurements conducted using a tube filled with both 18F and 68Ga to validate the obtained results. The MDA achieved for both anatomies (approximately 1000 kBq/mL for mice and 1 kBq/mL for humans) falls below the peak radiotracer concentrations typically found in PET studies, affirming the feasibility of conducting non-invasive AIF measurements with the fiber detector. The sensitivity for measurements with a tube filled with 18F (68Ga) was 1.2 (2.07) cps/(kBq/mL), while for simulations, it was 2.81 (6.23) cps/(kBq/mL). Further studies are needed to validate these results in pharmacokinetic PET studies.

The ER membrane protein complex restricts mitophagy by controlling BNIP3 turnover.

Lysosomal degradation of autophagy receptors is a common proxy for selective autophagy. However, we find that two established mitophagy receptors, BNIP3 and BNIP3L/NIX, are constitutively delivered to lysosomes in an autophagy-independent manner. This alternative lysosomal delivery of BNIP3 accounts for nearly all its lysosome-mediated degradation, even upon mitophagy induction. To identify how BNIP3, a tail-anchored protein in the outer mitochondrial membrane, is delivered to lysosomes, we performed a genome-wide CRISPR screen for factors influencing BNIP3 flux. This screen revealed both known modifiers of BNIP3 stability as well as a pronounced reliance on endolysosomal components, including the ER membrane protein complex (EMC). Importantly, the endolysosomal system and the ubiquitin-proteosome system regulated BNIP3 independently. Perturbation of either mechanism is sufficient to modulate BNIP3-associated mitophagy and affect underlying cellular physiology. More broadly, these findings extend recent models for tail-anchored protein quality control and install endosomal trafficking and lysosomal degradation in the canon of pathways that tightly regulate endogenous tail-anchored protein localization.

Side-Selective Solid-Phase Metallaphotoredox N(in)-Arylation of Peptides.

Postsynthetic diversification of peptides through selective modification of endogenous amino acid side chains has enabled significant advances in peptide drug discovery while expanding the biological and medical chemistry space. However, current tools have been focused on the modification of reactive polar and ionizable side chains, whereas the decoration of aromatic systems (e.g., the N(in) of the tryptophan) has been a long-standing challenge. Here, we introduce metallaphotocatalysis in solid-phase peptide synthesis for the on-resin orthogonal N-arylation of relevant tryptophan-containing peptides. The protocol allows the chemoselective introduction of a new C(sp2)-N bond at the N(in) of tryptophan in biologically active protected peptide sequences in the presence of native redox-sensitive side chains. The fusion of metallaphotocatalysis with solid-phase peptide synthesis opens new perspectives in diversifying native amino acid side chains.

Phosphoprotein phosphatase activity positively regulates oligomeric pyrin to trigger inflammasome assembly in phagocytes.

IMPORTANCE: Pyrin, a unique cytosolic receptor, initiates inflammatory responses against RhoA-inactivating bacterial toxins and effectors like Yersinia's YopE and YopT. Understanding pyrin regulation is crucial due to its association with dysregulated inflammatory responses, including Familial Mediterranean Fever (FMF), linked to pyrin gene mutations. FMF mutations historically acted as a defense mechanism against plague. Negative regulation of pyrin through PKN phosphorylation is well established, with Yersinia using the YopM effector to promote pyrin phosphorylation and counteract its activity. This study highlights the importance of phosphoprotein phosphatase activity in positively regulating pyrin inflammasome assembly in phagocytic cells of humans and mice. Oligomeric murine pyrin has S205 phosphorylated before inflammasome assembly, and this study implicates the dephosphorylation of murine pyrin S205 by two catalytic subunits of PP2A in macrophages. These findings offer insights for investigating the regulation of oligomeric pyrin and the balance of kinase and phosphatase activity in pyrin-associated infectious and autoinflammatory diseases.

Giant Mature Ovarian Cystic Teratoma in a Pediatric Patient: Case Report and Literature Review.

Mature cystic teratomas, also called dermoid cysts, are the most common germ-cell ovarian neoplasms in children. On average, ovarian dermoid cysts are slow-growing neoplasms with a mean size between 6.4 and 7.0 cm that enlarge at a rate of 1.8 mm/year; however, these can reach large dimensions. Giant ovarian tumors are defined as those having a maximum diameter equal to or more than 15 cm; these represent a therapeutic challenge as they increase the risk of wide wound size and surgical invasiveness. In this paper, we present a case of a 10-year-old Hispanic female that complained of abdominal pain, distension, and nausea. Physical examination revealed a mass on the left side of the abdomen and an axial computed tomography found a large pelvic tumor extending to the abdominal region. After a laparotomy approach, pathology evaluation confirmed the diagnosis of mature cystic teratoma. The patient recovered thoroughly and had no complications at a 6-month follow-up. We conducted a literature review including English and Spanish reports about giant ovarian teratomas; we retrieved 16 cases from 2003 to 2023. We concluded that giant ovarian tumors may be underreported, particularly in resource-limited areas where tumors might grow unrecognized, and that English-language bias might play a substantial role in literature reviews involving case reports and case series.

Hydrogen bonding patterns and C-H...π interactions in the structure of the antiparkinsonian drug (R)-rasagiline mesylate determined using laboratory and synchrotron X-ray powder diffraction data.

The structure of (R)-rasagiline mesylate [(R)-RasH+·Mes-], an active pharmaceutical ingredient used to treat Parkinson's disease, is presented. The structure was determined from laboratory and synchrotron powder diffraction data, refined using the Rietveld method, and validated and optimized using dispersion-corrected DFT calculations. The unit-cell parameters obtained in both experiments are in good agreement and the refinement with both datasets converged to good agreement factors. The final parameters obtained from laboratory data were a = 5.4905 (8), b = 6.536 (2), c = 38.953 (3) Å, V = 1398.0 (4) Å3 and from synchrotron powder data were a = 5.487530 (10) Å, b = 6.528939 (12) Å, c = 38.94313 (9) Å, V = 1395.245 (5) Å3 with Z = 4 and space group P212121. Preferred orientation was properly accounted for using the synchrotron radiation data, leading to a March-Dollase parameter of 1.140 (1) instead of the 0.642 (1) value obtained from laboratory data. In the structure, (R)-RasH+ moieties form layers parallel to the ab plane connected by mesylate ions through N-H...O and C-H...O hydrogen bonds. These layers stack along the c axis and are further connected by C-H...π interactions. Hirshfeld surface analysis and fingerprint plot calculations indicate that the main interactions are: H...H (50.9%), H...C/C...H (27.1%) and H...O/O...H (21.1%).

Combined Inhibition of Indolamine-2,3-Dioxygenase 1 and C-X-C Chemokine Receptor Type 2 Exerts Antitumor Effects in a Preclinical Model of Cervical Cancer.

Cervical cancer is a public health problem diagnosed in advanced stages, and its main risk factor is persistent high-risk human papillomavirus infection. Today, it is necessary to study new treatment strategies, such as immunotherapy, that use different targets of the tumor microenvironment. In this study, the K14E7E2 mouse was used as a cervical cancer model to evaluate the inhibition of indolamine-2,3-dioxygenase 1 (IDO-1) and C-X-C chemokine receptor type 2 (CXCR-2) as potential anti-tumor targets. DL-1MT and SB225002 were administered for 30 days in two regimens (R1 and R2) based on combination and single therapy approaches to inhibit IDO-1 and CXCR-2, respectively. Subsequently, the reproductive tracts were resected and analyzed to determine the tumor areas, and IHCs were performed to assess proliferation, apoptosis, and CD8 cellular infiltration. Our results revealed that combined inhibition of IDO-1 and CXCR-2 significantly reduces the areas of cervical tumors (from 196.0 mm2 to 58.24 mm2 in R1 and 149.6 mm2 to 52.65 mm2 in R2), accompanied by regions of moderate dysplasia, decreased papillae, and reduced inflammation. Furthermore, the proliferation diminished, and apoptosis and intra-tumoral CD8 T cells increased. In conclusion, the combined inhibition of IDO-1 and CXCR-2 is helpful in the antitumor response against preclinical cervical cancer.

Morphometric characterization and temporal temperature measurements during hepatic microwave ablation in swine.

PURPOSE: Heat-induced destruction of cancer cells via microwave ablation (MWA) is emerging as a viable treatment of primary and metastatic liver cancer. Prediction of the impacted zone where cell death occurs, especially in the presence of vasculature, is challenging but may be achieved via biophysical modeling. To advance and characterize thermal MWA for focal cancer treatment, an in vivo method and experimental dataset were created for assessment of biophysical models designed to dynamically predict ablation zone parameters, given the delivery device, power, location, and proximity to vessels. MATERIALS AND METHODS: MWA zone size, shape, and temperature were characterized and monitored in the absence of perfusion in ex vivo liver and a tissue-mimicking thermochromic phantom (TMTCP) at two power settings. Temperature was monitored over time using implanted thermocouples with their locations defined by CT. TMTCPs were used to identify the location of the ablation zone relative to the probe. In 6 swine, contrast-enhanced CTs were additionally acquired to visualize vasculature and absence of perfusion along with corresponding post-mortem gross pathology. RESULTS: Bench studies demonstrated average ablation zone sizes of 4.13±1.56cm2 and 8.51±3.92cm2, solidity of 0.96±0.06 and 0.99±0.01, ablations centered 3.75cm and 3.5cm proximal to the probe tip, and temperatures of 50 ºC at 14.5±13.4s and 2.5±2.1s for 40W and 90W ablations, respectively. In vivo imaging showed average volumes of 9.8±4.8cm3 and 33.2±28.4cm3 and 3D solidity of 0.87±0.02 and 0.75±0.15, and gross pathology showed a hemorrhagic halo area of 3.1±1.2cm2 and 9.1±3.0cm2 for 40W and 90W ablations, respectfully. Temperatures reached 50ºC at 19.5±9.2s and 13.0±8.3s for 40W and 90W ablations, respectively. CONCLUSION: MWA results are challenging to predict and are more variable than manufacturer-provided and bench predictions due to vascular stasis, heat-induced tissue changes, and probe operating conditions. Accurate prediction of MWA zones and temperature in vivo requires comprehensive thermal validation sets.

Soil Thermophiles and Their Extracellular Enzymes: A Set of Capabilities Able to Provide Significant Services and Risks.

During this century, a number of reports have described the potential roles of thermophiles in the upper soil layers during high-temperature periods. This study evaluates the capabilities of these microorganisms and proposes some potential consequences and risks associated with the activity of soil thermophiles. They are active in organic matter mineralization, releasing inorganic nutrients (C, S, N, P) that otherwise remain trapped in the organic complexity of soil. To process complex organic compounds in soils, these thermophiles require extracellular enzymes to break down large polymers into simple compounds, which can be incorporated into the cells and processed. Soil thermophiles are able to adapt their extracellular enzyme activities to environmental conditions. These enzymes can present optimum activity under high temperatures and reduced water content. Consequently, these microorganisms have been shown to actively process and decompose substances (including pollutants) under extreme conditions (i.e., desiccation and heat) in soils. While nutrient cycling is a highly beneficial process to maintain soil service quality, progressive warming can lead to excessive activity of soil thermophiles and their extracellular enzymes. If this activity is too high, it may lead to reduction in soil organic matter, nutrient impoverishment and to an increased risk of aridity. This is a clear example of a potential effect of future predicted climate warming directly caused by soil microorganisms with major consequences for our understanding of ecosystem functioning, soil health and the risk of soil aridity.

Eating in the city: Experimental effect of anthropogenic food resources on the body condition, nutritional status, and oxidative stress of an urban bioindicator passerine.

Urban areas provide a constant and predictable supply of anthropogenic processed food. The House Sparrow (Passer domesticus Linnaeus, 1758), a declining urban bioindicator species, has recently been reported to have a high level of oxidative stress, with urban diet or pollutants proposed as the potential cause. In this study, we aimed to experimentally determine the effects of two urban trophic resource types (bar snack food leftovers and pet food) on sparrows' physical condition, plasma biochemical nutritional parameters, and blood oxidative status in captivity. To exclude the potential previous effect of urban pollutants, 75 House Sparrows were captured from a rural area in SE Spain and kept in outdoor aviaries. Individuals were exposed to one of three diet treatments: control diet (fruit, vegetables, poultry grain mixture), bar snack diet (ultra-processed snacks), or cat food diet (dry pellets) for 20 days. Blood samples were collected before and after diet treatments to analyze the relative change rates of 12 variables, including physical condition, nutritional status, and oxidant-antioxidant status. A principal component analysis was run to identify gradients of variables covariation, and Generalized Linear Mixed Models were used to determine the effect of diets on each selected PC and on raw variables. The bar snack diet led to signs of anemia and malnutrition, and females tended to lose body condition. The cat food diet increased oxidative stress indicators and protein catabolism. Unbalanced urban diets can affect the body condition and nutritional physiology of House Sparrows and may also induce oxidative stress despite the absence of environmental pollution.

Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis.

FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS.

Functional vitamin B12 deficiency: Improving methylmalonic acid reference intervals in urine.

BACKGROUND-AIM: Most laboratory requests focus on the detection of possible vitamin B12 deficiency. In this context, methylmalonic acid (MMA) is reported as the best biomarker. The aim of our study was to establish the biological reference interval for MMA in urine, and assess the influence of age, sex, and vitamin B12 status on MMA concentrations. METHODS: This is a prospective observational study considering individuals with normal results for blood count and liver and kidney function. Individuals who presented supplementation, any pathology or treatment that could cause cobalamin metabolism disorders, and pregnant women were excluded. Likewise, individuals whose vitamin B12 result presented antibody-mediated interference were excluded. Individuals were grouped by age-group and sex. Reference intervals were determined by non-parametric calculation (percentiles 1-99). RESULTS: It was established a single reference interval [0.52 (CI90%: 0.50-0.54) - 5.75 (CI90%: 5.57-6.17) mmolMMA/mol creatinine], with 100 % of individuals with MMA above the upper limit of reference presenting a total vitamin B12 concentration ≤ 238 pmol/L. CONCLUSION: The establishment of optimal reference intervals for methylmalonic acid excretion in urine is crucial in individuals with a suspicion of functional vitamin B12 deficiency. However, the possibility of establishing a cut-off value for total vitamin B12 suggesting subclinical deficiency remains a challenge for this magnitude.

Photofunctional Scope of Fluorescent Dithienylethene Conjugates with Aza-Heteroaromatic Cations.

A series of dithienylethene (DTE) photoswitches with aza-heteroaromatic cationic moieties is synthesized. The switches are characterized regarding their photochemical and photophysical properties in acetonitrile and in water. The efficiency of the switching and the photostationary state composition depend on the degree of π-conjugation of the heteroaromatic systems. Thus, DTEs with acridinium-derived moieties have very low quantum yields for the ring-closing process, which is in contrast to switches with pyridinium and quinolinium moieties. All switches emit fluorescence in their open forms. The involved electronic transitions are traced back to an integrative picture including the DTE core and the cationic arms. The emission can be fine-tuned by the π-conjugation of the heteroaromatic cations, reaching the red spectral region for DTEs with acridinium moieties. On ring-closing of the DTEs the fluorescence is not observable anymore. Theoretical calculations point to rather low-lying energy levels of the highly conjugated ring-closed DTEs, which would originate near-infrared emission (> 1200 nm). The latter is predicted to be very weak due to the concurrent non-radiative deactivation, according to the energy-gap law. In essence, an ON-OFF fluorescence switching as the result of the electrocyclic ring-closing reaction is observed.

The ER membrane protein complex governs lysosomal turnover of a mitochondrial tail-anchored protein, BNIP3, to restrict mitophagy.

Lysosomal degradation of autophagy receptors is a common proxy for selective autophagy. However, we find that two established mitophagy receptors, BNIP3 and BNIP3L/NIX, violate this assumption. Rather, BNIP3 and NIX are constitutively delivered to lysosomes in an autophagy-independent manner. This alternative lysosomal delivery of BNIP3 accounts for nearly all of its lysosome-mediated degradation, even upon mitophagy induction. To identify how BNIP3, a tail-anchored protein in the outer mitochondrial membrane, is delivered to lysosomes, we performed a genome-wide CRISPR screen for factors influencing BNIP3 flux. By this approach, we revealed both known modifiers of BNIP3 stability as well as a pronounced reliance on endolysosomal components, including the ER membrane protein complex (EMC). Importantly, the endolysosomal system regulates BNIP3 alongside, but independent of, the ubiquitin-proteosome system (UPS). Perturbation of either mechanism is sufficient to modulate BNIP3-associated mitophagy and affect underlying cellular physiology. In short, while BNIP3 can be cleared by parallel and partially compensatory quality control pathways, non-autophagic lysosomal degradation of BNIP3 is a strong post-translational modifier of BNIP3 function. More broadly, these data reveal an unanticipated connection between mitophagy and TA protein quality control, wherein the endolysosomal system provides a critical axis for regulating cellular metabolism. Moreover, these findings extend recent models for tail-anchored protein quality control and install endosomal trafficking and lysosomal degradation in the canon of pathways that ensure tight regulation of endogenous TA protein localization.