Abstract
Mitochondria, the major source of cellular ATP, display high vulnerability to metabolic stress, in particular to excessive Ca2+ loading. Here, we show that Ca2+-inhibited mitochondrial ATP generation could be restored through stimulated Ca2+ discharge from mitochondrial matrix. This was demonstrated using a Ca2+ ionophore or through Na+/Ca2+ exchange-mediated decrease of mitochondrial Ca2+ load. Furthermore, diazoxide, a mitochondrial potassium channel opener, which maintained mitochondrial Ca2+ homeostasis, also restored Ca2+-inhibited ATP synthesis and preserved the structural integrity of Ca2+-challenged mitochondria. Thus, under conditions of excessive mitochondrial Ca2+ overload targeting mitochondrial Ca2+ transport pathways restores oxidative phosphorylation required for vital cellular processes. This study, therefore, identifies an effective strategy capable to rescue Ca2+-disrupted mitochondrial energetics.
Original language | English (US) |
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Pages (from-to) | 135-140 |
Number of pages | 6 |
Journal | Molecular and Cellular Biochemistry |
Volume | 220 |
Issue number | 1-2 |
DOIs | |
State | Published - 2001 |
Keywords
- ATP
- Bioenergetics
- Ca overload
- Cardioprotection
- Diazoxide
- Mitochondria
- Potassium channel opener
ASJC Scopus subject areas
- Molecular Biology
- Clinical Biochemistry
- Cell Biology