title: ROS act as an upstream signal to mediate cadmium-induced mitophagy in mouse brain.
abstract: As a well known generator of reactive oxygen species (ROS), cadmium (Cd) is found to be an effective inducer of mitophagy in mouse kidney and liver cells. Here, we aim to elucidate whether Cd can also initiate mitophagy in mouse brain and what role ROS play in this process. Our results showed that Cd caused overproduction of ROS. Meanwhile, Cd induced mitophagy, as indicated by the collapse of mitochondrial membrane potential (MMP), formation of mitophagosomes, increases of PINK1 level and LC3-II/LC3-I ratio and decrease of mitochondrial mass. Scavenging of ROS by N-acetyl-L-cysteine (NAC) or acetyl-L-carnitine (ALC) rescued MMP and mitochondrial mass, and squelched PINK1 level, mitochondrial accumulation of Parkin and LC3-II/LC3-I ratio, suggesting that ROS were associated with Cd-induced mitophagy. Cyclosporine A (CsA), an inhibitor of mitophagy, blocked Cd-induced mitophagy and PINK1/Parkin pathway but failed to suppress ROS increase, revealing that ROS are the causes rather than the results of Cd-induced mitophagy. In conclusion, this study suggested that ROS functioned on the upstream of PINK1/Parkin pathway to mediate Cd-induced mitophagy.
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wei
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Gu
authors.affiliation: Gansu Provincial Hospital, Lanzhou 730030, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, China. Electronic address: ymzhang@lzu.edu.cn.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002104:Cadmium / Q000633:toxicity*; D017364:Collagenases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D046529:Microscopy, Electron, Transmission; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C480860:Map1lc3b protein, mouse; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D002104:Cadmium; D000108:Acetylcarnitine; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D017364:Collagenases; D000111:Acetylcysteine
keywords: Brain; Cadmium; Mitophagy; Mouse; ROS