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PDMD: A complex II‐regulated form of mitochondrial dysfunction in metabolically exhausted cells
Author(s) -
Hawkins Brian John,
Petrenko Nataliya B,
Patel Vickas V,
Davis Christiana,
Madesh Muniswamy
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1017.5
Subject(s) - mitochondrion , depolarization , neurodegeneration , microbiology and biotechnology , biology , dnaja3 , membrane potential , electrochemical gradient , inner mitochondrial membrane , mitochondrial apoptosis induced channel , chemistry , mitochondrial fusion , biochemistry , biophysics , mitochondrial dna , medicine , gene , membrane , disease
Functional impairment of mitochondria contributes to many human diseases including myocardial infarction, stroke, cancer, aging and neurodegeneration. However, the underlying mechanisms of mitochondrial dysfunction are not well understood. Our studies elucidate a mode of mitochondrial depolarization that is independent of cyclophilin D, Bcl‐2 family proteins, extra mitochondrial energy, or high amplitude swelling. We termed this mode of mitochondrial dysfunction proton‐dependent mitochondrial depolarization (PDMD), which prominently manifests in ischemic cells. The evolutionarily conserved PDMD is dependent on dissipation of the mitochondrial proton gradient and can be solely reversed by the complex II substrate, succinate. Human fibroblasts lacking mitochondrial‐encoded complex I and F0F1‐ATPase subunits still maintain mitochondrial membrane potential by a complex II‐driven mechanism. This route of reversible mitochondrial functional impairment provides a potential target for the treatment of mitochondrial diseases and rejuvenation of exhausted cells in acute injury.