Intercellular Mitochondrial Transfer: The Novel Therapeutic Mechanism for Diseases.

Mitochondria, the dynamic organelles responsible for energy production and cellular metabolism, have the metabolic function of extracting energy from nutrients and synthesizing crucial metabolites. Nevertheless, recent research unveils that intercellular mitochondrial transfer by tunneling nanotubes, tumor microtubes, gap junction intercellular communication, extracellular vesicles, endocytosis and cell fusion may regulate mitochondrial function within recipient cells, potentially contributing to disease treatment, such as nonalcoholic steatohepatitis, glioblastoma, ischemic stroke, bladder cancer and neurodegenerative diseases. This review introduces the principal approaches to intercellular mitochondrial transfer and examines its role in various diseases. Furthermore, we provide a comprehensive overview of the inhibitors and activators of intercellular mitochondrial transfer, offering a unique perspective to illustrate the relationship between intercellular mitochondrial transfer and diseases.

Multiple functions of CALCOCO family proteins in selective autophagy.

Selective autophagy is the lysosomal degradation of specific intracellular components sequestered into autophagosomes, late endosomes, or lysosomes through the activity of selective autophagy receptors. CALCOCO family proteins are the newly found selective autophagy receptors, which include calcium binding and coiled-coil domain 1 (CALCOCO1), calcium binding and coiled-coil domain 2/nuclear domain 10 protein 52 (CALCOCO2/NDP52), and calcium binding and coiled-coil domain 3/Tax1-binding protein 1 (CALCOCO3/TAX1BP1). Specifically, CALCOCO1 can be recruited to endoplasmic reticulum (ER) and Golgi to mediate selective ER-phagy and Golgiphagy. CALCOCO2 and CALCOCO3, which are two essential cargo receptors, can mediate mitophagy and xenophagy through interacting with autophagy-related-8/microtubule-associated protein 1 light chain 3 (ATG8/LC3) on the growing autophagosome, and binding ubiquitin for cargo recruitment. Considering the significance of these proteins in selective autophagy, we review the structures, distribution, posttranslational modifications, and phylogenetic analysis of CALCOCO family proteins and their roles in different selective autophagy.

Apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy.

Cardiac hypertrophy is a leading cause of cardiac morbidity and mortality worldwide. Apelin is the endogenous ligand for the G protein-coupled receptor, APJ. Previously, we have revealed that apelin-13 can induce cardiomyocyte hypertrophy by activating the autophagy pathway. However, the precise mechanism through which apelin-13 regulates reticulophagy to participate in cardiomyocyte hypertrophy remains unclear. Herein, we observed that apelin-13-induced cardiomyocyte hypertrophy by activating FAM134B-dependent reticulophagy via the Pannexin-1/P2X7 signal pathway. Furthermore, we found that apelin-13 stimulated the opening of Pannexin-1 hemichannel and increased extracellular ATP (eATP) levels, which activated the P2X7 purinergic receptor. Activation of the Pannexin-1/eATP/P2X7 axis subsequently led to FAM134B-dependent reticulophagy. Moreover, inhibition of the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy reversed apelin-13-induced cardiomyocyte hypertrophy. Based on our present findings, apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy.

Laminar airflow ventilation systems in orthopaedic operating room do not prevent surgical site infections: a systematic review and meta-analysis.

BACKGROUND: Laminar airflow (LAF) technologies minimize infectious microorganisms to enhance air quality and surgical site infections (SSIs). LAF lowers SSIs in some clinical studies but not others. This study analyzes laminar airflow ventilation's capacity to reduce orthopaedic surgery-related SSIs. METHODS: The PRISMA-compliant keywords were utilized to conduct a search for pertinent articles in various databases including PubMed, MEDLINE, CENTRAL, Web of Sciences, and the Cochrane databases. Observational studies, including retrospective, prospective, and cohort designs, satisfy the PICOS criteria for research methodology. The assessment of quality was conducted utilizing the Robvis software, while the meta-analysis was performed using the RevMan application. The study's results were assessed based on effect sizes of odds ratio (OR) and risk ratio (RR). RESULTS: From 2000 to 2022, 10 randomized controlled clinical trials with 10,06,587 orthopaedic surgery patients met the inclusion criteria. The primary outcomes were: (1) Risk of SSI, (2) Bacterial count in sampled air and (3) Reduction in SSIs. The overall pooled OR of all included studies was 1.70 (95% CI 1.10-2.64), and the overall pooled RR was 1.27 (95% CI 1.02-1.59) with p < 0.05. LAF is ineffective at preventing SSIs in orthopaedic procedures due to its high-risk ratio and odds ratio. CONCLUSIONS: The present meta-analysis has determined that the implementation of LAF systems does not result in a significant reduction in the incidence of surgical site infections (SSIs), bacterial count in the air, or SSIs occurrence in orthopaedic operating rooms. Consequently, the installation of said equipment in operating rooms has been found to be both expensive and inefficient.

MCU-dependent mitochondrial calcium uptake-induced mitophagy contributes to apelin-13-stimulated VSMCs proliferation.

Apelin is an endogenous ligand of the G protein-coupled receptor APJ. Both apelin and APJ receptors, which are expressed in vascular smooth muscle cells (VSMCs), play important roles in the cardiovascular system. Our previous studies researches indicated that mitophagy mediated apelin-13-induced VSMCs proliferation. However, little is known about how apelin-13 regulates mitophagy to participate in VSMC proliferation. The results of the present study demonstrated that mitochondrial calcium uniporter (MCU) uptake-dependent mitochondrial calcium-induced mitophagy is involved in apelin-13-induced VSMCs proliferation. Apelin-13 promoted the expression of MCU which increases mitochondrial calcium uptake. Apelin-13-induced MCU-dependent mitochondrial calcium uptake further increased mitochondrial ROS (mtROS) concentrations and promoted mitophagy, which can be evidenced through the upregulation of the Dynamin-related protein 1(Drp1), PTEN-induced kinase 1 (PINK1), and Parkin. The clearance of mtROS by Mito-TEMPO significantly reversed apelin-13-induced mitophagy. Moreover, both the Drp1 inhibitor mdivi-1 and siRNA-Drp1 inhibited apelin-13-induced mitophagy. Furthermore, the APJ receptor antagonist F13A, MCU inhibitor Ru360, mitochondria-targeted antioxidant Mito-TEMPO, Drp1 inhibitor Mdivi-1, siRNA-Drp1, siRNA-PINK1, and siRNA-Parkin inhibited the proliferation of VSMCs induced by apelin-13. In ApoE-/- mice, intraperitoneal administration of apelin-13 induced the expression of MCU, Drp1, PINK1, Parkin, and α-SMA and increased atherosclerotic plaque lesions. However, F13A and Ru360 decreased the expression of MCU, Drp1, PINK1, Parkin, and α-SMA and reduced atherosclerotic plaque lesions in ApoE-/- mice injected with apelin-13. Collectively, our results demonstrate that MCU-dependent mitochondrial calcium uptake-induced mitophagy is involved in apelin-13-stimulated VSMCs proliferation.