Lead (Pb), a widely distributed environmental pollutant, is known to induce mitochondrial damage as well as autophagy in vitro and in vivo. In this study, we found that Pb could trigger mitophagy in both HEK293 cells and the kidney cortex of male Kunming mice. However, whether ataxia telangiectasis mutated (ATM) which is reported to be linked with PTEN-induced putative kinase 1 (PINK1)/Parkin pathway (a well-characterized mitophagic pathway) participates in the regulation of Pb-induced mitophagy and its exact role remains enigmatic. Our results indicated that Pb activated ATM in vitro and in vivo, and further in vitro studies showed that ATM could co-localize with PINK1 and Parkin in cytosol and interact with PINK1. Knockdown of ATM by siRNA blocked Pb-induced mitophagy even under the circumstance of enhanced accumulation of PINK1 and mitochondrial Parkin. Intriguingly, elevation instead of reduction in phosphorylation level of PINK1 and Parkin was observed in response to ATM knockdown and Pb did not contribute to the further increase of their phosphorylation level, implying that ATM indirectly regulated PINK1/Parkin pathway. These findings reveal a novel mechanism for Pb toxicity and suggest the regulatory importance of ATM in PINK1/Parkin-mediated mitophagy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.toxlet.2018.04.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Fasting enhances the efficacy of Sorafenib in breast cancer via mitophagy mediated ROS-driven p53 pathway.
Free Radic Biol Med
January 2025
Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, Rehabilitation Medicine Center, West China Hospital, Sichuan University /West China School of Nursing, Sichuan University, Chengdu, 610041, China; Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:
The multi-kinase inhibitor sorafenib has shown potential to inhibit tumor cell growth and intra-tumoral angiogenesis by targeting several kinases, including VEGFR2 and RAF. Abnormal activation of the Ras/Raf/MAPK/ERK kinase cascade and the VEGF pathway is a common feature in breast cancer. However, the efficacy of sorafenib in breast cancer treatment remains limited.
View Article and Find Full Text PDFA novel strategy for the protective effect of ginsenoside Rg1 against ovarian reserve decline by the PINK1 pathway.
Pharm Biol
December 2025
The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China.
Context: The decline in ovarian reserve is a major concern in female reproductive health, often associated with oxidative stress and mitochondrial dysfunction. Although ginsenoside Rg1 is known to modulate mitophagy, its effectiveness in mitigating ovarian reserve decline remains unclear.
Objective: To investigate the role of ginsenoside Rg1 in promoting mitophagy to preserve ovarian reserve.
Autophagy and Mitophagy in Diabetic Kidney Disease-A Literature Review.
Int J Mol Sci
January 2025
Department of Nephrology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania.
Autophagy and mitophagy are critical cellular processes that maintain homeostasis by removing damaged organelles and promoting cellular survival under stress conditions. In the context of diabetic kidney disease, these mechanisms play essential roles in mitigating cellular damage. This review provides an in-depth analysis of the recent literature on the relationship between autophagy, mitophagy, and diabetic kidney disease, highlighting the current state of knowledge, existing research gaps, and potential areas for future investigations.
View Article and Find Full Text PDFThe P2X7-Mediated Mitochondrial ROS as an Emerging Core Target of Tuftsin Nanoparticles in Severe Acute Pancreatitis Therapy via Regulating Mitophagy.
ACS Appl Mater Interfaces
January 2025
Department of Gerontology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People's Republic of China.
20% acute pancreatitis (AP) develops into severe AP (SAP), a global health crisis, with an increased mortality rate to 30%-50%. Mitochondrial damage and immune disorders are direct factors, which exacerbate the occurrence and progression of AP. So far, mitochondrial and immunity injury in SAP remains largely elusive, with no established treatment options available.
View Article and Find Full Text PDFAkkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer's disease pathologic process via GPR41 and GPR43.
Microbiome
January 2025
Innovative Institute of Animal Health Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangdong Province, Guangzhou, 510025, China.
Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disease (ND). In recent years, multiple clinical and animal studies have shown that mitochondrial dysfunction may be involved in the pathogenesis of AD. In addition, short-chain fatty acids (SCFA) produced by intestinal microbiota metabolism have been considered to be important factors affecting central nervous system (CNS) homeostasis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!