Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor.

The removal of unwanted or damaged mitochondria by autophagy, a process called mitophagy, is essential for key events in development, cellular homeostasis, tumor suppression, and prevention of neurodegeneration and aging. However, the precise mechanisms of mitophagy remain uncertain. Here, we identify the inner mitochondrial membrane protein, prohibitin 2 (PHB2), as a crucial mitophagy receptor involved in targeting mitochondria for autophagic degradation. PHB2 binds the autophagosomal membrane-associated protein LC3 through an LC3-interaction region (LIR) domain upon mitochondrial depolarization and proteasome-dependent outer membrane rupture. PHB2 is required for Parkin-induced mitophagy in mammalian cells and for the clearance of paternal mitochondria after embryonic fertilization in C. elegans. Our findings pinpoint a conserved mechanism of eukaryotic mitophagy and demonstrate a function of prohibitin 2 that may underlie its roles in physiology, aging, and disease.

Fanconi Anemia Proteins Function in Mitophagy and Immunity.

Fanconi anemia (FA) pathway genes are important tumor suppressors whose best-characterized function is repair of damaged nuclear DNA. Here, we describe an essential role for FA genes in two forms of selective autophagy. Genetic deletion of Fancc blocks the autophagic clearance of viruses (virophagy) and increases susceptibility to lethal viral encephalitis. Fanconi anemia complementation group C (FANCC) protein interacts with Parkin, is required in vitro and in vivo for clearance of damaged mitochondria, and decreases mitochondrial reactive oxygen species (ROS) production and inflammasome activation. The mitophagy function of FANCC is genetically distinct from its role in genomic DNA damage repair. Moreover, additional genes in the FA pathway, including FANCA, FANCF, FANCL, FANCD2, BRCA1, and BRCA2, are required for mitophagy. Thus, members of the FA pathway represent a previously undescribed class of selective autophagy genes that function in immunity and organellar homeostasis. These findings have implications for understanding the pathogenesis of FA and cancers associated with mutations in FA genes.

EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance.

Cell surface growth factor receptors couple environmental cues to the regulation of cytoplasmic homeostatic processes, including autophagy, and aberrant activation of such receptors is a common feature of human malignancies. Here, we defined the molecular basis by which the epidermal growth factor receptor (EGFR) tyrosine kinase regulates autophagy. Active EGFR binds the autophagy protein Beclin 1, leading to its multisite tyrosine phosphorylation, enhanced binding to inhibitors, and decreased Beclin 1-associated VPS34 kinase activity. EGFR tyrosine kinase inhibitor (TKI) therapy disrupts Beclin 1 tyrosine phosphorylation and binding to its inhibitors and restores autophagy in non-small-cell lung carcinoma (NSCLC) cells with a TKI-sensitive EGFR mutation. In NSCLC tumor xenografts, the expression of a tyrosine phosphomimetic Beclin 1 mutant leads to reduced autophagy, enhanced tumor growth, tumor dedifferentiation, and resistance to TKI therapy. Thus, oncogenic receptor tyrosine kinases directly regulate the core autophagy machinery, which may contribute to tumor progression and chemoresistance.

Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism.

The molecular mechanism of autophagy and its relationship to other lysosomal degradation pathways remain incompletely understood. Here, we identified a previously uncharacterized mammalian-specific protein, Beclin 2, which, like Beclin 1, functions in autophagy and interacts with class III PI3K complex components and Bcl-2. However, Beclin 2, but not Beclin 1, functions in an additional lysosomal degradation pathway. Beclin 2 is required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) through its interaction with GASP1. Beclin 2 homozygous knockout mice have decreased embryonic viability, and heterozygous knockout mice have defective autophagy, increased levels of brain cannabinoid 1 receptor, elevated food intake, and obesity and insulin resistance. Our findings identify Beclin 2 as a converging regulator of autophagy and GPCR turnover and highlight the functional and mechanistic diversity of Beclin family members in autophagy, endolysosomal trafficking, and metabolism.

Target genes regulated by CLEC16A intronic region associated with common variable immunodeficiency.

BACKGROUND: CLEC16A intron 19 has been identified as a candidate locus for common variable immunodeficiency (CVID). OBJECTIVES: This study sought to elucidate the molecular mechanism by which variants at the CLEC16A intronic locus may contribute to the pathogenesis of CVID. METHODS: The investigators performed fine-mapping of the CLEC16A locus in a CVID cohort, then deleted the candidate functional SNP in T-cell lines by the CRISPR-Cas9 technique and conducted RNA-sequencing to identify target gene(s). The interactions between the CLEC16A locus and its target genes were identified using circular chromosome conformation capture. The transcription factor complexes mediating the chromatin interactions were determined by proteomic approach. The molecular pathways regulated by the CLEC16A locus were examined by RNA-sequencing and reverse phase protein array. RESULTS: This study showed that the CLEC16A locus is an enhancer regulating expression of multiple target genes including a distant gene ATF7IP2 through chromatin interactions. Distinct transcription factor complexes mediate the chromatin interactions in an allele-specific manner. Disruption of the CLEC16A locus affects the AKT signaling pathway, as well as the molecular response of CD4+ T cells to immune stimulation. CONCLUSIONS: Through multiomics and targeted experimental approaches, this study elucidated the underlying target genes and signaling pathways involved in the genetic association of CLEC16A with CVID, and highlighted plausible molecular targets for developing novel therapeutics.

Projection of Mortality Burden Attributable to Nonoptimum Temperature with High Spatial Resolution in China.

The updated climate models provide projections at a fine scale, allowing us to estimate health risks due to future warming after accounting for spatial heterogeneity. Here, we utilized an ensemble of high-resolution (25 km) climate simulations and nationwide mortality data from 306 Chinese cities to estimate death anomalies attributable to future warming. Historical estimation (1986-2014) reveals that about 15.5% [95% empirical confidence interval (eCI):13.1%, 17.6%] of deaths are attributable to nonoptimal temperature, of which heat and cold corresponded to attributable fractions of 4.1% (eCI:2.4%, 5.5%) and 11.4% (eCI:10.7%, 12.1%), respectively. Under three climate scenarios (SSP126, SSP245, and SSP585), the national average temperature was projected to increase by 1.45, 2.57, and 4.98 °C by the 2090s, respectively. The corresponding mortality fractions attributable to heat would be 6.5% (eCI:5.2%, 7.7%), 7.9% (eCI:6.3%, 9.4%), and 11.4% (eCI:9.2%, 13.3%). More than half of the attributable deaths due to future warming would occur in north China and cardiovascular mortality would increase more drastically than respiratory mortality. Our study shows that the increased heat-attributable mortality burden would outweigh the decreased cold-attributable burden even under a moderate climate change scenario across China. The results are helpful for national or local policymakers to better address the challenges of future warming.

Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.

Autophagy increases the lifespan of model organisms; however, its role in promoting mammalian longevity is less well-established1,2. Here we report lifespan and healthspan extension in a mouse model with increased basal autophagy. To determine the effects of constitutively increased autophagy on mammalian health, we generated targeted mutant mice with a Phe121Ala mutation in beclin 1 (Becn1F121A/F121A) that decreases its interaction with the negative regulator BCL2. We demonstrate that the interaction between beclin 1 and BCL2 is disrupted in several tissues in Becn1 F121A/F121A knock-in mice in association with higher levels of basal autophagic flux. Compared to wild-type littermates, the lifespan of both male and female knock-in mice is significantly increased. The healthspan of the knock-in mice also improves, as phenotypes such as age-related renal and cardiac pathological changes and spontaneous tumorigenesis are diminished. Moreover, mice deficient in the anti-ageing protein klotho 3 have increased beclin 1 and BCL2 interaction and decreased autophagy. These phenotypes, along with premature lethality and infertility, are rescued by the beclin 1(F121A) mutation. Together, our data demonstrate that disruption of the beclin 1-BCL2 complex is an effective mechanism to increase autophagy, prevent premature ageing, improve healthspan and promote longevity in mammals.

Author Correction: Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.

In this Letter, the graphs in Fig. 2a and c were inadvertently the same owing to a copy and paste error from the original graphs in Prism. The Source Data files containing the raw data were correct. Fig. 2c has been corrected online.

Regulation of Notch Signaling Pathway to Innate Lymphoid Cells in Patients with Acute Myocardial Infarction.

The Notch signaling pathway is an important regulator in fate decisions and immune responses of innate lymphoid cells (ILCs). However, the function of Notch signaling in ILCs in acute coronary syndrome is still not fully elucidated. Thirty-one unstable angina pectoris (UAP) patients, 21 acute myocardial infarction (AMI) patients, and 20 controls were included in this study. Peripheral blood mononuclear cells (PBMCs) were isolated. The mRNA expression levels of Notch receptors and ligands were measured by real-time PCR, while ILC subsets were measured by flow cytometry. Lin- cells were purified and stimulated with γ-secretase inhibitor (GSI). ILC subsets, transcription factors, and secreted cytokines were assessed. Notch receptor and ligand mRNA levels were elevated in PBMCs and peripheral lin- cells from AMI patients. There was no significant difference in total lin-CD45+CD161+CD127+ ILC frequency among three groups. The CRTH2-CD117- ILC1 subset was down-regulated, while the CRTH2+ ILC2 subset was up-regulated in AMI patients. The CRTH2-CD117+ ILC3 subpopulation was comparable among the three groups. ILC1% was negatively correlated with Notch1 and Notch2 in AMI patients. Inhibition of Notch signaling pathway by GSI induced elevations in ILC1 frequency, T-bet mRNA expression, and interferon-γ secretion and reduced ILC2 frequency, GATA3 mRNA levels, and interleukin-5/interleukin-13 production by lin- cells from AMI patients. The current data indicated that activation of Notch signaling pathway might contribute to ILC1-to-ILC2 shift in peripheral blood in AMI patients.

PDK1 Regulates the Lengthening of G1 Phase to Balance RGC Proliferation and Differentiation during Cortical Neurogenesis.

During cortical development, the balance between progenitor self-renewal and neurogenesis is critical for determining the size/morphology of the cortex. A fundamental feature of the developing cortex is an increase in the length of G1 phase in RGCs over the course of neurogenesis, which is a key determinant of progenitor fate choice. How the G1 length is temporally regulated remains unclear. Here, Pdk1, a member of the AGC kinase family, was conditionally disrupted by crossing an Emx1-Cre mouse line with a Pdk1fl/fl line. The loss of Pdk1 led to a shorter cell cycle accompanied by increased RGC proliferation specifically at late rather than early/middle neurogenic stages, which was attributed to impaired lengthening of G1 phase. Coincidently, apical-to-basal interkinetic nuclear migration was accelerated in Pdk1 cKO cortices. Consequently, we detected an increased neuronal output at P0. We further showed the significant upregulation of the cell cycle regulator cyclin D1 and its activator Myc in the cKO cortices relative to those of control animals. Overall, we have identified a novel role for PDK1 in cortical neurogenesis. PDK1 functions as an upstream regulator of the Myc-cyclin D1 pathway to control the lengthening of G1 phase and the balance between RGC proliferation and differentiation.

Characteristics and determinants of personal exposure to typical air pollutants: A pilot study in Beijing and Baoding, China.

Personal exposure to fine particulate matter (PM2.5), nitrogen oxides (NOx, NO2 and NO), ozone (O3) and sulfur dioxide (SO2) was repeatedly measured among fourteen office workers in Beijing and Baoding, China in summer, autumn and winter of 2019. Time-activity patterns were simultaneously recorded. Determinants of personal air pollution exposure were investigated for each pollutant via a linear mixed effect model. The personal concentrations of PM2.5, NO2, NO and O3 were higher in autumn and winter than those in summer. A decreasing trend was found in the personal PM2.5 level for a typical indoor population in Beijing, indicating that particulate pollution was effectively controlled in Beijing and its surrounding area. The personal levels of PM2.5, NO2, and O3 were weakly correlated with those monitored at ambient stations and were lower than the respective ambient levels except for PM2.5 in summer and NO2 in winter. This pilot study showed that the indoor air environment, ambient pollution, traffic-related variables and temperature were significant exposure sources for office workers. Our study highlighted the significance of controlling traffic emissions and improving the workplace air quality to protect the health of office workers. More importantly, we demonstrated the feasibility of model development for personal air pollution exposure prediction.

Association of long-term air pollution exposure with the risk of prediabetes and diabetes: Systematic perspective from inflammatory mechanisms, glucose homeostasis pathway to preventive strategies.

BACKGROUND: Limited evidence suggests the association of air pollutants with a series of diabetic cascades including inflammatory pathways, glucose homeostasis disorder, and prediabetes and diabetes. Subclinical strategies for preventing such pollutants-induced effects remain unknown. METHODS: We conducted a cross-sectional study in two typically air-polluted Chinese cities in 2018-2020. One-year average PM1, PM2.5, PM10, SO2, NO2, and O3 were calculated according to participants' residence. GAM multinomial logistic regression was performed to investigate the association of air pollutants with diabetes status. GAM and quantile g-computation were respectively performed to investigate individual and joint effects of air pollutants on glucose homeostasis markers (glucose, insulin, HbA1c, HOMA-IR, HOMA-B and HOMA-S). Complement C3 and hsCRP were analyzed as potential mediators. The ABCS criteria and hemoglobin glycation index (HGI) were examined for their potential in preventive strategy. RESULTS: Long-term air pollutants exposure was associated with the risk of prediabetes [Prevalence ratio for O3 (PR_O3) = 1.96 (95% CI: 1.24, 3.03)] and diabetes [PR_PM1 = 1.18 (95% CI: 1.05, 1.32); PR_PM2.5 = 1.08 (95% CI: 1.00, 1.16); PR_O3 = 1.35 (95% CI: 1.03, 1.74)]. PM1, PM10, SO2 or O3 exposure was associated with glucose-homeostasis disorder. For example, O3 exposure was associated with increased levels of glucose [7.67% (95% CI: 1.75, 13.92)], insulin [19.98% (95% CI: 4.53, 37.72)], HOMA-IR [34.88% (95% CI: 13.81, 59.84)], and decreased levels of HOMA-S [-25.88% (95% CI: -37.46, -12.16)]. Complement C3 and hsCRP played mediating roles in these relationships with proportion mediated ranging from 6.95% to 60.64%. Participants with HGI ≤ -0.53 were protected from the adverse effects of air pollutants. CONCLUSION: Our study provides comprehensive insights into air pollutant-associated diabetic cascade and suggests subclinical preventive strategies.

Personal PM2.5-bound PAH exposure and lung function in healthy office workers: A pilot study in Beijing and Baoding, China.

The effect of short-term exposure to polycyclic aromatic hydrocarbons (PAHs) on the respiratory system among healthy residents is unclear. Beijing and Baoding are typical polluted cities in China, and there is little research on PAH exposure and its health effects at the individual level. Fourteen healthy female office workers were recruited in urban Beijing and Baoding, China, in 2019. The personal exposure to fine particulate matter (PM2.5)-bound PAHs and lung function were seasonally monitored. The relationships between PAH exposure and lung function were determined by a generalized mixed linear model. Subjects were exposed to high levels of PAH, in which the benzo[a]pyrene (BaP) level (1.26 ng/m3) was over than Chinese national indoor standard (1 ng/m3). All PAHs concentration was higher in winter than that in summer and autumn. Only benz[a]anthracene (BaA) and chrysene (Chr) exposure showed weak relations with decreased lung function, i.e., a 0.58% and 0.73% decrease in peak expiratory flow at lag 2 day, respectively (p < 0.05). PAHs may not be suitable exposure indicators for short-term change in lung function. Our findings highlight the importance of reducing PAH pollution for public respiratory health protection in heavy-polluted cities of China. This pilot study also provides experience on personal PAH assessment such as estimation of the number of repeated measurements required, which is helpful to determine the relationship between PAH exposure and health effect.

Risk of neurodegeneration among residents of electronic waste recycling areas.

The abnormal disposal process of electronic waste (e-waste) always emits a variety of toxic substances that enter the human body through various environmental media and can have many adverse health effects. Metals are thought to be inextricably linked to neurodegeneration. In the present study, we tried to explore the neurodegenerative status of subjects exposed to e-waste and the association between metal intake and neurodegeneration. We recruited the residents near the e-waste recycling area (the exposed group) and the residents without any e-waste contact history (the reference group) for a comparative study with detection and analysis of metals, biomarkers associated with neurodegeneration or oxidative stress (OS). The results showed that the metals between the reference and exposed group were significantly different. The concentrations of Brain-derived neurotrophic factor (BDNF) and ß-amyloid protein 42 (Aß42) in the exposed groups were significantly lower, while the levels of Euchromatic Histone lysine Methyltransferase 1 (EHMT1), Bromodomain Adjacent to Zinc finger domain 2B (BAZ2B) and Malondialdehyde (MDA) were significantly higher than in the reference groups. Although the ratio of Aß42/Aß40 had no statistical significance in the two groups, the medians of the ratio in the exposed group was lower than in the reference group. The linear regression and mediating effect analysis showed that MDA (OS) might mediate the effects of metals on EHMT1(pAg-MDA <0.001, pMDA-EHMT1 <0.05, pAg-EHMT1 <0.001). It could be inferred from the results of the present investigation that e-waste exposure had a high risk of neurodegeneration, especially Sliver (Ag) and Nickel (Ni).

Acute effects of exposure to fine particulate matter and ozone on lung function, inflammation and oxidative stress in healthy adults.

Both fine particulate matter (PM2.5) and ozone (O3) may have adverse effects on human health. However, previous studies on the effects of air pollutants mainly have focused on susceptible population, and evidence on healthy young adults is limited. We aimed to examine the associations of the two main air pollutants (PM2.5 and O3) with lung function, inflammation and oxidative stress in healthy young adults. We recruited 30 healthy young adults for a longitudinal panel study in Beijing and implemented health examination seven times, including lung function (FEV1 and PEF) and biomarkers of inflammation and oxidative stress (i.e. C-reactive protein, CRP; interleukin-6, IL-6; malondialdehyde, MDA) from December 2019 to May 2021. Hourly ambient air pollutants data were obtained from the closest air quality monitoring station. Linear mixed-effect model was applied to explore the associations between air pollutants and lung function, inflammation and oxidative stress. We observed higher PM2.5 exposure was associated with decrement in lung function and increment in CRP and MDA. Each 10 µg/m3 increase in PM2.5 (lag 2 day) is associated with a 17.06 ml (95% CI: -31.53, -2.58) decrease in FEV1, 46.34 ml/s (95% CI: -76.41, -16.27) decrease in PEF and increments of 2.86% (95% CI: 1.47%, 4.27%) in CRP, 1.63% (95% CI: 0.14%, 3.14%) in MDA respectively. However, there is no significant association between ozone exposure and health indicators. The study suggested that short-term exposure to PM2.5 may decrease lung function and induce inflammation and oxidative stress in healthy adults, but there is no association between O3 and each outcome.

The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance.

BACKGROUND: Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche. RESULTS: In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies. CONCLUSIONS: These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.

PDK1 Regulates Transition Period of Apical Progenitors to Basal Progenitors by Controlling Asymmetric Cell Division.

The six-layered neocortex consists of diverse neuron subtypes. Deeper-layer neurons originate from apical progenitors (APs), while upper-layer neurons are mainly produced by basal progenitors (BPs), which are derivatives of APs. As development proceeds, an AP generates two daughter cells that comprise an AP and a deeper-layer neuron or a BP. How the transition of APs to BPs is spatiotemporally regulated is a fundamental question. Here, we report that conditional deletion of phoshpoinositide-dependent protein kinase 1 (PDK1) in mouse developing cortex achieved by crossing Emx1Cre line with Pdk1fl/fl leads to a delayed transition of APs to BPs and subsequently causes an increased output of deeper-layer neurons. We demonstrate that PDK1 is involved in the modulation of the aPKC-Par3 complex and further regulates the asymmetric cell division (ACD). We also find Hes1, a downstream effecter of Notch signal pathway is obviously upregulated. Knockdown of Hes1 or treatment with Notch signal inhibitor DAPT recovers the ACD defect in the Pdk1 cKO. Thus, we have identified a novel function of PDK1 in controlling the transition of APs to BPs.

Cobalt exposure increases the risk of fibrosis of people living near E­waste recycling area.

The toxicity of heavy metals is one of the major public health issues leading to hazardous effects on humans. Many studies focus on the adverse effects on people who were working in or living near E-waste recycling. However, little is known to the sustaining effects of E-waste exposure on human health after the recycling factories were shut down. In the present study, we collected the blood of people living near E­waste recycling facilities after the recycling factories were closed for 2 years. Eight heavy metals were examined in all blood samples. The results revealed that the blood levels of lead (Pb), nickel (Ni), cobalt (Co), mercury (Hg) were significantly higher in the exposed group than in the reference group, and no difference was observed for copper (Cu), zinc (Zn), stannum (Sn), cadmium (Cd). Transforming growth factor-ß (TGF-ß) and alpha-smooth muscle actin (α-SMA) were analyzed as the important indicators of fibrosis, which were statistically significantly higher in the exposed group than in the reference group. 8-isoprostane (8-I) and malondialdehyde (MDA) as the biomarkers of oxidative stress (OS) were elevated in the exposed group. Furthermore, both Spearman correlation and multiple linear regression showed that Co was positively correlated with TGF-ß, α-SMA and 8-I in the exposed group. Accordingly, we speculate that high concentrations of Co dissolved in the blood may increase the risk of tissue fibrosis through stimulating myofibroblast activation and OS involve in the process, which may provide some potential new hints for the intervention for tissue fibrosis in the future.

The changes of essential trace elements in residents from an e-waste site and the relationships between elements and hormones of the hypothalamic-pituitary-thyroid (HPT) axis.

The heavy metals pollution and related health issues were widely reported in e-waste sites, while the impacts of e-waste exposure on the essential trace elements have been neglected. The aim of this study was focused on the internal Cu, Fe, Mn and Zn levels in the residents from an e-waste site and the potential endocrine disrupting effects of these essential trace elements on the hypothalamic-pituitary-thyroid (HPT) axis. This was a cross-sectional study that 87 subjects were recruited from the e-waste site and 81 from the reference site. The results indicated that the e-waste exposed group had significantly lower Fe, Mn level when compared with the reference group (p < 0.05). Cu and Zn were also lower in the exposed group but the differences were not statistically significant. The exposed group had significantly higher TSH level and Fe was significantly associated with TSH in the females (ß (95% CI): - 1.892 (-3.309, -0.475), p = 0.009), rather than in males or all subjects. The exposed group also showed oxidative stress which was indicated by the increased concentrations of MDA and 8-iso-PG. It was further indicated the elevated MDA was mediated by the increase of TSH in the females but not directly related to Fe. In conclusion, the e-waste exposed group showed a decrease of essential trace elements, an increase of TSH and oxidative stress. The decreased Fe was related to the elevated TSH in the females, which further indirectly mediated the increase of oxidative stress. The results suggested that the internal exposure levels and the potential health effects of the essential trace elements in populations from e-waste sites should be of more concern. And the women might be more vulnerable and they need more protection to against the adverse health effects from e-waste.

Size distribution of particulate polycyclic aromatic hydrocarbons in fresh combustion smoke and ambient air: A review.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the atmosphere and they mostly stem from the imperfect combustion of fossil fuels and biofuels. PAHs are inherently associated with homogenous fine particles or distributed to different-sized particles during the aging of air masses. PAHs carried by fine particles undergo a long-range transport to remote areas while those adsorbed on coarse particles have a shorter lifetime in ambient air. More importantly, PAHs with higher molecular weights tend to be bound with finer particles and can deeply enter the lungs, posing severe health risks to humans. Thus, the environmental fate and health effects of particulate PAHs are strongly size-dependent. This review summarizes the size distributions of particulate PAHs freshly emitted from combustion sources as well as the distribution patterns of PAHs in ambient particles. It was found that PAHs from stationary sources are primarily bound to fine particles, which are slightly larger than particles to which PAHs from mobile sources are bound. In ambient air, particulate PAHs are distributed in larger size modes than those in the combustion fume, and the particle size decreases with PAH molecular weight increasing. The relevant mechanisms and influencing factors of particle size distribution changes are illustrated in this article, which are essentially attributed to combustion and ambient temperature as well as the physical and chemical properties of PAHs. Overall, the study on the particle size distribution of PAHs will contribute for a full understanding of the origin, atmospheric behaviors and health effects of particulate PAHs.