| Senescence, or the loss of growth potential, is invariably related to mitochondrial dysfunction in the filamentous fungus Neurospora crassa. The mitochondrial dysfunction is often due to the effects of mitochondrial plasmids. The variant forms of the Mauriceville mitochondrial plasmid cause senescence by integrating into the mitochondrial genome or over-replicating, disrupting the mitochondrial genes or their synthesis. The strain which senesces due to plasmid over-replication is predicted to have a mutation involved in the Integration of the plasmid, Recombination or Selection of defective mitochondria (IRS).;The two forms of senescence are analogous to two sources of mitochondrial dysfunction in human disease: the inhibition of mitochondrial translation and the propagation of mitochondrial DNA deletions. The transcriptional profiles of the two models of senescence reveal many similarities to mitochondrial damage responses in higher organisms, suggesting that N. crassa is a good model for mitochondrial diseases. The use of RNA-Sequencing to generate the transcriptional profiles, provides the sequences of transcribed genes along with the relative gene expression. The comparison of the sequences generated from cultures approaching senescence to healthy cultures suggests significant changes to genome stability. This would indicate that the nuclear genome could adapt to mitochondrial damage over time.;The genetic analysis of plasmid-containing strains which escape senescence indicates that two mutations are required for longevity. One of the mutations associated with the Long-lived strain, that escapes senescence, is in a gene which regulates the expression of alternative oxidase (AOX). AOX is induced by mitochondrial dysfunction, including the over-replication of the plasmd. |
