The mitochondrial genome is more damage-prone than the nuclear genome, at least in part to damage caused by the generation of a superoxide in the electron transport chain. For hyphal growth to continue, functional mitochondria must continuously replace mitochondria damaged by harmful reactive oxygen species. Since mitochondrial proteins are encoded by mitochondrial and nuclear genomes, the renewal of functional mitochondria requires the integrated action of both the nucleus and the mitochondria. Unexpectedly, the studies of senescence in fungi form a basis for the endosymbiont hypothesis of eukaryotic cells. It is conceivable that during evolution, the transfer of genes encoding mitochondrial proteins protecting the mitochondrial genome were transferred from mitochondria to the nucleus. Cloning and identification of nd+ or sen+ gene products will have implications in understanding not only the assembly of mitochondria in eukaryotic cells but also in understanding human mitochondrial diseases due to mutation in nuclear genes. Among the several possibilities are nuclear gene-encoded factors that protect the mitochondrial genome from deletions and recombination events that could occur by default. Alternatively, a nuclear gene mutation that affects the assembly of the multiprotein mitochondrial machinery that translocates proteins from the cytosol into the mitochondria, known as the translocase of outer membrane (TOM) and translocase of inner membrane (TIM), will be at a severe disadvantage in the cell and affect viability. Another possibility is that because of the presence of repeat elements, mitochondrial DNA is inherently prone to intramolecular recombination and deletions and requires "protection" by protein factors. In the course of evolution of eukaryotes, the genes encoding the protective factors could have transferred from the mitochondria to the nucleus. The senescing strains of fungi offer unique opportunities for assessing postulated free radical hypothesis and uncovering supplemental hypotheses of aging and death in higher organisms.
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