Substrate-dependent and cyclophilin D-independent regulation of mitochondrial flashes in skeletal and cardiac muscle

التفاصيل البيبلوغرافية
العنوان: Substrate-dependent and cyclophilin D-independent regulation of mitochondrial flashes in skeletal and cardiac muscle
المؤلفون: Lan Wei-LaPierre, Alina Ainbinder, Robert T. Dirksen, Kevin M. Tylock
المصدر: Archives of Biochemistry and Biophysics. 665:122-131
بيانات النشر: Elsevier BV, 2019.
سنة النشر: 2019
مصطلحات موضوعية: 0301 basic medicine, Biophysics, Oxidative phosphorylation, Biochemistry, Article, Substrate Specificity, 03 medical and health sciences, medicine, Animals, Myocyte, Glycolysis, Muscle, Skeletal, Molecular Biology, Mice, Knockout, Membrane potential, 030102 biochemistry & molecular biology, Chemistry, Myocardium, Cardiac muscle, Skeletal muscle, Depolarization, Mitochondria, Muscle, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Mitochondrial matrix, Cyclophilin D
الوصف: Mitochondrial flashes (mitoflashes) are stochastic events in the mitochondrial matrix detected by mitochondrial-targeted cpYFP (mt-cpYFP). Mitoflashes are quantal bursts of reactive oxygen species (ROS) production accompanied by modest matrix alkalinization and depolarization of the mitochondrial membrane potential. Mitoflashes are fundamental events present in a wide range of cell types. To date, the precise mechanisms for mitoflash generation and termination remain elusive. Transient opening of the mitochondrial membrane permeability transition pore (mPTP) during a mitoflash is proposed to account for the mitochondrial membrane potential depolarization. Here, we set out to compare the tissue-specific effects of cyclophilin D (CypD)-deficiency and mitochondrial substrates on mitoflash activity in skeletal and cardiac muscle. In contrast to previous reports, we found that CypD knockout did not alter the mitoflash frequency or other mitoflash properties in acutely isolated cardiac myocytes, skeletal muscle fibers, or isolated mitochondria from skeletal muscle and the heart. However, in skeletal muscle fibers, CypD deficiency resulted in a parallel increase in both activity-dependent mitochondrial Ca2+ uptake and activity-dependent mitoflash activity. Increases in both mitochondrial Ca2+ uptake and mitoflash activity following electrical stimulation were abolished by inhibition of mitochondrial Ca2+ uptake. We also found that mitoflash frequency and amplitude differ greatly between intact skeletal muscle fibers and cardiac myocytes, but that this difference is absent in isolated mitochondria. We propose that this difference may be due, in part, to differences in substrate availability in intact skeletal muscle fibers (primarily glycolytic) and cardiac myocytes (largely oxidative). Overall, we find that CypD does not contribute significantly in mitoflash biogenesis under basal conditions in skeletal and cardiac muscle, but does regulate mitoflash events during muscle activity. In addition, tissue-dependent differences in mitoflash frequency are strongly regulated by mitochondrial substrate availability.
تدمد: 0003-9861
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6330608a34dbe8477cf851a20002e925Test
https://doi.org/10.1016/j.abb.2019.03.003Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....6330608a34dbe8477cf851a20002e925
قاعدة البيانات: OpenAIRE