title: Mitochondrial CCAR2/DBC1 is required for cell survival against rotenone-induced mitochondrial stress.
abstract: CCAR2 (cell cycle and apoptosis regulator protein 2; formerly DBC1, deleted in breast cancer 1) functions in diverse cellular processes including responses to genotoxic and metabolic stresses. However, its role in the mitochondrial stress response has not been fully elucidated. To investigate how CCAR2 regulates stress response, we purified CCAR2-containing complexes. Interestingly, the results revealed that CCAR2 localized to the mitochondria, and also bound Hsp60 (heat shock protein 60), a mitochondrial chaperone. The binding of CCAR2 to Hsp60 increased following rotenone-induced mitochondrial stress. The deficiencies in CCAR2 and Hsp60 also disrupted the mitochondrial membrane potential, thereby promoting apoptosis following mitochondrial stress. In summary, the CCAR2-Hsp60 complex promoted cell survival during mitochondrial stress-induced apoptosis. These data suggest that CCAR2 is critical for maintaining mitochondrial homeostasis in response to stress.
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Wootae
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Min Gyeong
authors.initials: MG
authors.lastname: Cheon
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: jekim@khu.ac.kr.
authors.forename: Ja-Eun
authors.initials: JE
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D011485:Protein Binding / Q000187:drug effects; D034622:RNA Interference; D012402:Rotenone / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: C112308:BRINP1 protein, human; D018797:Cell Cycle Proteins; D018834:Chaperonin 60; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D014475:Uncoupling Agents; D012402:Rotenone
keywords: Apoptosis; CCAR2; Hsp60; Mitochondria