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Poster

Mitochondrial NM23-H4/NDPK-D Supports Cardiolipin Signaling to Eliminate Depolarized Mitochondria by Mitophagy

Abstract : The well-established function of the hexameric intermembrane space protein, NDPK-D/NM23-H4, is phosphotransfer activity as a nucleoside diphosphate kinase. However, recent data revealed a second function in lipid signaling that is involved in mitophagy, a critical process for cell homeostasis. Externalization of the inner mitochondrial membrane phospholipid, cardiolipin (CL), to the mitochondrial surface was identified as a mitophageal signal, recognized by the microtubule-associated protein 1 light chain 3. Here we demonstrate that NDPK-D binds CL and facilitates its re-distribution to the outer mitochondrial membrane. We found that mitophagy induced by a protonophoric uncoupler, CCCP, caused externalization of CL to the surface of mitochondria in murine lung epithelial MLE-12 cells and human cervical adenocarcinoma HeLa cells. RNAi knockdown of endogenous NDPK-D decreased CCCP-induced CL externalization and mitochondrial degradation. A R90D NDPK-D mutant which does not bind CL was inactive in promoting mitophagy. In situ proximity ligation assay showed that mitophagy-inducing CL transfer activity of NDPK-D is closely associated with the dynamin-like GTPase OPA1, and OPA1 silencing favored NDPK-D supported CL transfer, implicating fission-fusion dynamics in mitophagy regulation.
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https://hal.univ-grenoble-alpes.fr/hal-01954186
Contributeur : Sarah Hamant <>
Soumis le : jeudi 13 décembre 2018 - 15:16:40
Dernière modification le : jeudi 8 octobre 2020 - 03:25:52

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Uwe Schlattner, Jianfei Jiang, Zhentai Huang, Yulia Tyurina, Céline Desbourdes, et al.. Mitochondrial NM23-H4/NDPK-D Supports Cardiolipin Signaling to Eliminate Depolarized Mitochondria by Mitophagy. 60th Annual Meeting of Biophysical Society, Feb 2016, Los Ageles, United States. 110 (3 suppl 1), pp.472a, 2016, Biophysical Journal. ⟨10.1016/j.bpj.2015.11.2528⟩. ⟨hal-01954186⟩

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