BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver.
Autophagy
; 17(11): 3530-3546, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-33459136
ABSTRACT
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; mtDNAnucDNA, ratio of mitochondrial DNA to nuclear DNA; PV, periportal vein; TOMM20, translocase of outer mitochondrial membrane protein 20.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Mitocondriais
/
Mitofagia
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Fígado
/
Proteínas de Membrana
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Proteínas Associadas aos Microtúbulos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article