Relationship Between Glycine Cytoprotection and the Mitochondrial Permeability Transition During Hypoxic Cell Injury

摘要

The studies supported by this grant have shown that, during hypoxia/ reoxygenation injury, mitochondria of kidney proximal tubule cells develop a profound functional deficit despite prevention of lethal plasma membrane damage by glycine. This is related to a persistent electron transport block at Site I. The mitochondria remain energized, but to a reduced degree. The lesion precedes development of the mitochondrial permeability transition and/or release of cytochrome c and is relatively stable. It can be prevented by mitochondrial permeability transition inhibitors and is even more potently prevented and reversed by substrates that contribute to anaerobic, intramitochondrial, substrate level phosphorylation or that can bypass, during reoxygenation, the block at Site I.