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Mitochondrial NM23-H4/NDPK-D and OPA1: Partners in Shaping Mitochondria and Initiating Mitophagy?

Abstract : The well-established function of the mitochondrial intermembrane space protein NM23-H4/NDPK-D is phosphotransfer activity as a nucleoside diphosphate kinase (NDPK). However, recent data have revealed a second function in lipid signaling that triggers mitophagy, a critical process for cell homeostasis (1,2). This latter function involves NM23-H4-mediated intermembrane transfer of cardiolipin (CL) from the mitochondrial inner membrane to the mitochondrial surface. Interestingly, both functions seem to involve an interaction of NM23-H4 with OPA1, a dynamin-like GTPase of the mitochondrial inner membrane. First, NM23-H4 directly fuels OPA1 with GTP via its NDPK bioenergetic function (3). In addition, also the CL transfer activity of NM23-H4 seems to depend on OPA1, since knock-down of OPA1 in HeLa cells reduces CL transfer in NM23-H4 WT expressing cells as compared to those expressing CL-transfer incompetent NM23-H4 mutants. Thus, OPA1 seems to be a negative regulator of the CL transfer function of NM23-H4. Our current model suggests that NM23-H4/OPA1 complexes exist in healthy mitochondria at the inner membrane to maintain OPA1 functions in membrane fusion and dynamics. Upon OPA1 cleavage, an early step during mitophagy, NM23-H4 may be released from these complexes, allowing simultaneous interaction of the hexameric NM23-H4 complex with inner and outer mitochondrial membrane and CL transfer.
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Contributeur : Sarah Hamant <>
Soumis le : jeudi 13 décembre 2018 - 13:37:45
Dernière modification le : jeudi 30 juillet 2020 - 03:00:24

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Uwe Schlattner, Céline Desbourdes, Malgorzata Tokarska-Schlattner, Valerian Kagan. Mitochondrial NM23-H4/NDPK-D and OPA1: Partners in Shaping Mitochondria and Initiating Mitophagy?. 58th Annual Meeting of the Biophysical Society, Feb 2014, San Francisco, United States. 112 (3 suppl 1), pp.324A-325A, 2017, Biophysical Journal. ⟨10.1016/j.bpj.2016.11.1757⟩. ⟨hal-01953990⟩



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