Dataset Information

NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia

ABSTRACT: NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Yi-Ju Chen

LAB HEAD: Zee-Fen Chang

PROVIDER: PXD049224 | Pride | 2026-02-23

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	YJC_NTU_20230314_DDA_3_wtMice.mzML	Mzml
	YJC_NTU_20230314_DDA_3_wtMice.raw	Raw
	YJC_NTU_20230314_DDA_4_mutMice.mzML	Mzml
	YJC_NTU_20230314_DDA_4_mutMice.raw	Raw
	YJC_NTU_20230314_DDA_NME3.msf	Msf

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Publications

NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia.

Chen Chih-Wei CW Su Chi C Huang Chang-Yu CY Huang Xuan-Rong XR Cuili Xiaojing X Chao Tung T Fan Chun-Hsiang CH Ting Cheng-Wei CW Tsai Yi-Wei YW Yang Kai-Chien KC Yeh Ti-Yen TY Hsieh Sung-Tsang ST Chen Yi-Ju YJ Feng Yuxi Y Hunter Tony T Chang Zee-Fen ZF

Nature communications 20240313 1

NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals ...[more]

PMID: 38480688

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