粒体自噬
生物
自噬
细胞生物学
线粒体
胞浆
转位酶
胰高血糖素
细胞凋亡
生物化学
基因
激素
染色体易位
酶
作者
Maya Z. Springer,Logan P. Poole,Lauren E. Drake,Althea Bock-Hughes,Michelle L. Boland,Alexandra G Smith,John Hart,Aparajita H. Chourasia,Ivan Liu,Grazyna Bozek,Kay F. Macleod
出处
期刊:Autophagy
[Informa]
日期:2021-02-08
卷期号:17 (11): 3530-3546
被引量:33
标识
DOI:10.1080/15548627.2021.1877469
摘要
Mitophagy formed the basis of the original description of autophagy by Christian de Duve when he demonstrated that GCG (glucagon) induced macroautophagic/autophagic turnover of mitochondria in the liver. However, the molecular basis of liver-specific activation of mitophagy by GCG, or its significance for metabolic stress responses in the liver is not understood. Here we show that BNIP3 is required for GCG-induced mitophagy in the liver through interaction with processed LC3B; an interaction that is also necessary to localize LC3B out of the nucleus to cytosolic mitophagosomes in response to nutrient deprivation. Loss of BNIP3-dependent mitophagy caused excess mitochondria to accumulate in the liver, disrupting metabolic zonation within the liver parenchyma, with expansion of zone 1 metabolism at the expense of zone 3 metabolism. These results identify BNIP3 as a regulator of metabolic homeostasis in the liver through its effect on mitophagy and mitochondrial mass distribution.Abbreviations: ASS1, arginosuccinate synthetase; BNIP3, BCL2/adenovirus E1B interacting protein 3; CV, central vein; GCG - glucagon; GLUL, glutamate- ammonia ligase (glutamine synthetase); HCQ, hydroxychloroquine; LIR, LC3-interacting region; MAP1LC3B/LC3B, microtubule-associated protein 1 light chain 3 beta; mtDNA:nucDNA, ratio of mitochondrial DNA to nuclear DNA; PV, periportal vein; TOMM20, translocase of outer mitochondrial membrane protein 20.
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