PMID- 30348987 OWN - NLM STAT- MEDLINE DCOM- 20191016 LR - 20191016 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Oct 22 TI - In vitro rejuvenation of brain mitochondria by the inhibition of actin polymerization. PG - 15585 LID - 10.1038/s41598-018-34006-5 [doi] LID - 15585 AB - The oxygen consumption rate (OCR) and cytochrome c oxidase (CcO) activity of respiratory complex IV (CIV) in brain mitochondria significantly decline in middle-aged male mice compared to younger male mice. To explore the mechanisms underlying the regulation of brain mitochondrial function, we examined CIV-associated proteins, and identified actin inside the isolated brain mitochondria. Inhibiting actin polymerization using cytochalasin B (CB) significantly enhanced the OCR and CcO activity of CIV in the mitochondria. These changes were accompanied by a significant reduction in the amount of CIV-bound cytochrome c (cyt c). Actin was also associated with respiratory complex III (CIII); however, the amount of CIII-bound cyt c increased significantly after treatment of the mitochondria with CB. In contrast, no significant alteration in the assembly or the CcO activity of CIV in CIV-containing supercomplexes or CIV monomers was induced by CB. These results suggest that mitochondrial actin plays a crucial role in the regulation of the CcO activity and OCR of CIV with modification of the retention of cyt c between CIV and CIII. FAU - Takahashi, Kazuhide AU - Takahashi K AD - Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0015, Japan. FAU - Miura, Yuri AU - Miura Y AD - Proteome Research, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0015, Japan. FAU - Ohsawa, Ikuroh AU - Ohsawa I AD - Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0015, Japan. FAU - Shirasawa, Takuji AU - Shirasawa T AD - Shirasawa Anti-Aging Medical Institute, Bunkyo, Tokyo, 113-0033, Japan. FAU - Takahashi, Mayumi AU - Takahashi M AD - Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0015, Japan. mmtaka@tmig.or.jp. LA - eng PT - Journal Article DEP - 20181022 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Actins) RN - 3CHI920QS7 (Cytochalasin B) RN - EC 1.9.3.1 (Electron Transport Complex IV) SB - IM MH - Actins/antagonists & inhibitors/*metabolism MH - Animals MH - Brain/growth & development/*metabolism MH - Cytochalasin B/pharmacology MH - Electron Transport Complex IV/metabolism MH - Male MH - Mice MH - Mitochondria/drug effects/*metabolism MH - Oxygen Consumption MH - Polymerization PMC - PMC6197264 COIS- The authors declare no competing interests. EDAT- 2018/10/24 06:00 MHDA- 2019/10/17 06:00 PMCR- 2018/10/22 CRDT- 2018/10/24 06:00 PHST- 2018/05/17 00:00 [received] PHST- 2018/10/07 00:00 [accepted] PHST- 2018/10/24 06:00 [entrez] PHST- 2018/10/24 06:00 [pubmed] PHST- 2019/10/17 06:00 [medline] PHST- 2018/10/22 00:00 [pmc-release] AID - 10.1038/s41598-018-34006-5 [pii] AID - 34006 [pii] AID - 10.1038/s41598-018-34006-5 [doi] PST - epublish SO - Sci Rep. 2018 Oct 22;8(1):15585. doi: 10.1038/s41598-018-34006-5.