H

H2O Pi ATP

Figure 14.13 Mitochondrial respiratory assemblies that transfer electrons to oxygen. AOX, alternative oxidase, SHAM, salicyl hydroxamate.

role in protecting against the lethal effects of ROS, and (iv) well-developed genetic and molecular techniques, this fungus provided a particularly good system for assessing the role of cytochrome-mediated respiration on the shortening of the life-span. The functional cytochrome gene was replaced by transformation with a plasmid construct that contained cytochrome oxidase gene lacking 169 bp of COX5 gene. Homologous replacement of the functional wild COX5 gene by a defective copy of a synthetic gene prevented the accumulation of senDNAs, decreased the formation of ROS and increased the life span of the fungus. Reintroduction of functional COX5 gene into the deleted strain restored the original phenotype, i.e., the original growth rate, reduced life-span, loss of fertility and increased formation of ROS without the accumulation of senDNAs. The authors hypothesized that aerobic respiration mediated by cytochrome oxidase is the general cause of aging and senescence of eukaryotic organisms. The experimental results favor the free radical theory of aging.

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