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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / deficiency
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy
  • Cell Line
  • Dynamins / chemistry
  • Dynamins / metabolism
  • Gene Knockdown Techniques
  • Gene Knockout Techniques
  • Homeostasis
  • Humans
  • Membrane Proteins / metabolism
  • Mice
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics*
  • Mitochondrial Proteins / metabolism
  • Phosphorylation
  • Protein Biosynthesis*
  • Protein Transport
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins
  • Ribosomal Proteins / deficiency
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Serine / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • DAP3 protein, human
  • Membrane Proteins
  • Mff protein, human
  • Mitochondrial Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • Serine
  • Dnm1l protein, mouse
  • Dynamins