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J Biol Chem. 2015 Oct 9;290(41):24961-74. doi: 10.1074/jbc.M115.673343. Epub 2015 Aug 25.

Death-associated Protein 3 Regulates Mitochondrial-encoded Protein Synthesis and Mitochondrial Dynamics.

Author information

1
From the Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543.
2
the Neuroscience and Behavioural Disorders Program, Duke-NUS Graduate Medical School, Singapore 169857, the NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117573.
3
the NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117573, the Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, and.
4
the Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
5
From the Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543, the NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117573, dbslyc@nus.edu.sg.

Abstract

Mitochondrial morphologies change over time and are tightly regulated by dynamic machinery proteins such as dynamin-related protein 1 (Drp1), mitofusion 1/2, and optic atrophy 1 (OPA1). However, the detailed mechanisms of how these molecules cooperate to mediate fission and fusion remain elusive. DAP3 is a mitochondrial ribosomal protein that involves in apoptosis, but its biological function has not been well characterized. Here, we demonstrate that DAP3 specifically localizes in the mitochondrial matrix. Knockdown of DAP3 in mitochondria leads to defects in mitochondrial-encoded protein synthesis and abnormal mitochondrial dynamics. Moreover, depletion of DAP3 dramatically decreases the phosphorylation of Drp1 at Ser-637 on mitochondria, enhancing the retention time of Drp1 puncta on mitochondria during the fission process. Furthermore, autophagy is inhibited in the DAP3-depleted cells, which sensitizes cells to different types of death stimuli. Together, our results suggest that DAP3 plays important roles in mitochondrial function and dynamics, providing new insights into the mechanism of a mitochondrial ribosomal protein function in cell death.

KEYWORDS:

Drp1, DAP3; autophagy; cell death; cell signaling; metabolism; mitochondria

PMID:
26306039
PMCID:
PMC4599003
DOI:
10.1074/jbc.M115.673343
[Indexed for MEDLINE]
Free PMC Article

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