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Mitochondrial CCAR2/DBC1 is required for cell survival against rotenone-induced mitochondrial stress

Wootae Kim1, Min Gyeong Cheon1, Ja-Eun Kim2

  • 1Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Biochemical and Biophysical Research Communications
|March 4, 2017
PubMed

Insights

Cell cycle and apoptosis regulator protein 2 (CCAR2) protects cells from mitochondrial stress. CCAR2 binds heat shock protein 60, promoting survival during apoptosis.

Area of Science:

  • Mitochondrial Biology
  • Cellular Stress Response
  • Apoptosis Regulation

Background:

  • Cell cycle and apoptosis regulator protein 2 (CCAR2), also known as deleted in breast cancer 1 (DBC1), is involved in cellular responses to genotoxic and metabolic stresses.
  • The specific role of CCAR2 in the mitochondrial stress response remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function of CCAR2 in regulating the cellular response to mitochondrial stress.
  • To elucidate the molecular mechanisms by which CCAR2 influences mitochondrial homeostasis and apoptosis.

Main Methods:

  • Purification of CCAR2-containing protein complexes.
  • Localization studies of CCAR2 within the cell.
  • Analysis of CCAR2-Hsp60 interaction under rotenone-induced mitochondrial stress.
  • Assessment of mitochondrial membrane potential and apoptosis in CCAR2 and Hsp60 deficient cells.

Main Results:

  • CCAR2 was found to localize to mitochondria and interact with the mitochondrial chaperone heat shock protein 60 (Hsp60).
  • The binding between CCAR2 and Hsp60 was significantly enhanced upon rotenone-induced mitochondrial stress.
  • Deficiencies in CCAR2 or Hsp60 led to disrupted mitochondrial membrane potential and increased apoptosis following stress.

Conclusions:

  • The CCAR2-Hsp60 complex plays a crucial role in promoting cell survival during mitochondrial stress-induced apoptosis.
  • CCAR2 is essential for maintaining mitochondrial homeostasis under conditions of cellular stress.
Keywords:
ApoptosisCCAR2Hsp60Mitochondria

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