PMID- 20347716 OWN - NLM STAT- MEDLINE DCOM- 20110110 LR - 20211020 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1797 IP - 6-7 DP - 2010 Jun-Jul TI - Regulation of mitochondrial fission by intracellular Ca2+ in rat ventricular myocytes. PG - 913-21 LID - 10.1016/j.bbabio.2010.03.018 [doi] AB - Mitochondria are dynamic organelles that constantly undergo fission, fusion, and movement. Increasing evidence indicates that these dynamic changes are intricately related to mitochondrial function, suggesting that mitochondrial form and function are linked. Calcium (Ca2+) is one signal that has been shown to both regulate mitochondrial fission in various cell types and stimulate mitochondrial enzymes involved in ATP generation. However, although Ca2+ plays an important role in adult cardiac muscle cells for excitation-metabolism coupling, little is known about whether Ca2+ can regulate their mitochondrial morphology. Therefore, we tested the role of Ca2+ in regulating cardiac mitochondrial fission. We found that neonatal and adult cardiomyocyte mitochondria undergo rapid and transient fragmentation upon a thapsigargin (TG)- or KCl-induced cytosolic Ca2+ increase. The mitochondrial fission protein, DLP1, participates in this mitochondrial fragmentation, suggesting that cardiac mitochondrial fission machinery may be regulated by intracellular Ca2+ signaling. Moreover, the TG-induced fragmentation was also associated with an increase in reactive oxygen species (ROS) formation, suggesting that activation of mitochondrial fission machinery is an early event for Ca2+-mediated ROS generation in cardiac myocytes. These results suggest that Ca2+, an important regulator of muscle contraction and energy generation, also dynamically regulates mitochondrial morphology and ROS generation in cardiac myocytes. CI - Copyright (c) 2010 Elsevier B.V. All rights reserved. FAU - Hom, Jennifer AU - Hom J AD - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. FAU - Yu, Tianzheng AU - Yu T FAU - Yoon, Yisang AU - Yoon Y FAU - Porter, George AU - Porter G FAU - Sheu, Shey-Shing AU - Sheu SS LA - eng GR - DK 61991/DK/NIDDK NIH HHS/United States GR - R01 HL033333-21/HL/NHLBI NIH HHS/United States GR - HL 33333/HL/NHLBI NIH HHS/United States GR - R01 HL033333/HL/NHLBI NIH HHS/United States GR - R01 DK061991/DK/NIDDK NIH HHS/United States GR - R01 HL093671-01A1/HL/NHLBI NIH HHS/United States GR - R01 HL093671/HL/NHLBI NIH HHS/United States GR - R01 DK061991-06A2/DK/NIDDK NIH HHS/United States GR - DK 73858/DK/NIDDK NIH HHS/United States GR - R21 DK073858-02/DK/NIDDK NIH HHS/United States GR - R01 DK078618/DK/NIDDK NIH HHS/United States GR - R21 DK073858/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20100327 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Microtubule-Associated Proteins) RN - 0 (Mitochondrial Proteins) RN - 0 (Reactive Oxygen Species) RN - 11062-77-4 (Superoxides) RN - 67526-95-8 (Thapsigargin) RN - EC 3.6.1.- (GTP Phosphohydrolases) RN - EC 3.6.5.5 (Dnm1l protein, rat) RN - EC 3.6.5.5 (Dynamins) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Animals, Newborn MH - Calcium/*metabolism MH - Calcium Signaling/drug effects MH - Cells, Cultured MH - Dynamins MH - GTP Phosphohydrolases/metabolism MH - In Vitro Techniques MH - Microscopy, Electron, Transmission MH - Microtubule-Associated Proteins/metabolism MH - Mitochondria, Heart/drug effects/*metabolism/ultrastructure MH - Mitochondrial Proteins/metabolism MH - Myocytes, Cardiac/drug effects/*metabolism/ultrastructure MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - Superoxides/metabolism MH - Thapsigargin/pharmacology PMC - PMC2891135 MID - NIHMS199418 EDAT- 2010/03/30 06:00 MHDA- 2011/01/11 06:00 PMCR- 2011/06/01 CRDT- 2010/03/30 06:00 PHST- 2009/12/01 00:00 [received] PHST- 2010/03/19 00:00 [revised] PHST- 2010/03/19 00:00 [accepted] PHST- 2010/03/30 06:00 [entrez] PHST- 2010/03/30 06:00 [pubmed] PHST- 2011/01/11 06:00 [medline] PHST- 2011/06/01 00:00 [pmc-release] AID - S0005-2728(10)00124-6 [pii] AID - 10.1016/j.bbabio.2010.03.018 [doi] PST - ppublish SO - Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):913-21. doi: 10.1016/j.bbabio.2010.03.018. Epub 2010 Mar 27.