Lack of mitochondrial DNA impairs chemical hypoxia-induced autophagy in liver tumor cells through ROS-AMPK-ULK1 signaling dysregulation independently of HIF-1α

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• 作者：Jose J.G. Marin^a ; Elisa Lozano^a ; Maria J. Perez^a ; ^b ; ^{mjperez@usal.es}
• 关键词：Akt ; protein kinase B ; AMPK ; AMP-activated protein kinase ; AVOs ; acidic vesicular organelles ; BNIP3 ; BCL2/adenovirus E1B 19  ; kDa interacting protein 3 ; BNIP3L ; BCL2/adenovirus E1B 19  ; kDa interacting protein 3-like ; CCND1 ; cyclin D1 ; CFSE ; 5-(6)-carboxyfluorescein diacetate succinimidyl ester ; CQ ; chloroquine ; CHOP ; C/EBP homologous protein ; CoCl2 ; cobalt chloride ; DCFH-DA ; 2&prime ; 7&prime ; -dichlorofluorescein diacetate ; DFO ; deferoxamine ; ER ; endoplasmic reticulum ; ERK ; extracellular r
• 刊名：Free Radical Biology and Medicine
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：101
• 期：Complete
• 页码：71-84
• 全文大小：3037 K
• 卷排序：101

文摘

Hypoxia mimetic agents increase transcriptionally active HIF-1α in mtDNA-depleted cells. MtDNA depletion impairs chemical hypoxia-induced autophagy by dysregulating AMPK. AMPK activation by chemical hypoxia-induced ROS is blocked in cells lacking mtDNA. CoCl2 and DFO-induced autophagy is involved in cell survival and death, respectively. MtDNA-deficient cells are resistant to CoCl2-induced endoplasmic reticulum stress.