title: Central role of Nix in the autophagic response to ochratoxin A.
abstract: Nephrotoxicity is the most prominent toxicological effects of ochratoxin A (OTA). We have previously shown that autophagy might be involved in OTA-induced early renal cytotoxicity, but the mechanisms of action are unknown. Since OTA is known to induce mitochondrial damage and Nix is a selective autophagy receptor for mitochondrial clearance, the objective of this study was to investigate whether Nix mediates autophagic response to OTA-induced renal cytotoxicity. Our results showed that OTA induced autophagic and mitophagic activitits. Nix shRNA HEK 293 cells were more sensitive than scrambled shRNA cells to OTA-induced cell death, and differentially affect the mRNA expression of SDHA, AIFM1, and Bad and protein expression of AIF, VDAC, SDHA and LONP1 after OTA treatment. In particular, up-regulation of the pro-apoptotic Bad and AIF after OTA treatment was prominent only in Nix shRNA cells, which might explain the higher ratio of cell death. These results might indicate that Nix plays a critical role in the cellular protection against OTA toxicity through autophagy and mitochondria.
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China; School of Public Health, Zunyi Medical University, Zunyi, Guizhou 563003, PR China.
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Shen
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Boyang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.affiliation: Department of Food Science, Nutrition and Health Promotion, Mississippi State University, MS 39762, USA.
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China. Electronic address: xuwentao@cau.edu.cn.
authors.forename: Wentao
authors.initials: W
authors.lastname: Xu
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: YunBo
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA.
authors.forename: Changhui
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Kunlun
authors.initials: K
authors.lastname: Huang
mesh_terms: D049069:ATP-Dependent Proteases / Q000378:metabolism; D051033:Apoptosis Inducing Factor / Q000235:genetics; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D042963:Electron Transport Complex II / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects; D009793:Ochratoxins / Q000633:toxicity*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; C494819:BAD protein, human; C116838:BNIP3L protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009793:Ochratoxins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D050994:Voltage-Dependent Anion Channels; D051025:bcl-Associated Death Protein; C025589:ochratoxin A; D042963:Electron Transport Complex II; C511268:SDHA protein, human; D049069:ATP-Dependent Proteases; C000595973:LONP1 protein, human
keywords: Apoptosis; Autophagy; Mitophagy; Ochratoxin A; Renal cytotoxicity