Alternative Oxidase Dependent Respiration Leads to an Increased Mitochondrial Content in Two Long-Lived Mutants of the Ageing Model Podospora anserina

Abstract

The retrograde response constitutes an important signalling pathway from mitochondria to the nucleus which induces several genes to allow compensation of mitochondrial impairments. In the filamentous ascomycete Podospora anserina, an example for such a response is the induction of a nuclear-encoded and iron-dependent alternative oxidase (AOX) occurring when cytochrome-c oxidase (COX) dependent respiration is affected. Several long-lived mutants are known which predominantly or exclusively respire via AOX. Here we show that two AOX-utilising mutants, grisea and PaCox17::ble, are able to compensate partially for lowered OXPHOS efficiency resulting from AOX-dependent respiration by increasing mitochondrial content. At the physiological level this is demonstrated by an elevated oxygen consumption and increased heat production. However, in the two mutants, ATP levels do not reach WT levels. Interestingly, mutant PaCox17::ble is characterized by a highly increased release of the reactive oxygen species (ROS) hydrogen peroxide. Both grisea and PaCox17::ble contain elevated levels of mitochondrial proteins involved in quality control, i. e. LON protease and the molecular chaperone HSP60. Taken together, our work demonstrates that AOX-dependent respiration in two mutants of the ageing model P. anserina is linked to a novel mechanism involved in the retrograde response pathway, mitochondrial biogenesis, which might also play an important role for cellular maintenance in other organisms.

A Differential Genome-Wide Transcriptome Analysis: Impact of Cellular Copper on Complex Biological Processes like Aging and Development

“…This was correlated with an increased oxygen consumption and greater mitochondrial mass suggesting that during the years of sub-cultivation in the laboratory a compensatory effect occurred [33]. The transcriptome data do not demonstrate a clear correlation of transcript levels, the mode of respiration and of compensatory effects due to an energetically less efficient alternative respiration.…”

Autophagy compensates impaired energy metabolism in CLPXP‐deficient Podospora anserina strains and extends healthspan

“…Normally, wild‐type strains of P. anserina respire via a standard cytochrome‐ c oxidase (COX, complex IV)‐dependent respiratory chain. However, when this pathway is impaired for any reason, a compensating mechanism is induced leading to the expression of a gene coding for an alternative oxidase (AOX; Borghouts et al ., ; Scheckhuber et al ., ). To elucidate the contribution of these two terminal oxidases in the ∆PaClpXP mutant, we measured the ratio between complex IV (C IV)‐ and AOX‐dependent OCR in mycelia of both strains.…”

Alternative Oxidase: A Mitochondrial Respiratory Pathway to Maintain Metabolic and Signaling Homeostasis during Abiotic and Biotic Stress in Plants

“…In extant prokaryotes, AOX is limited to some α-proteobacteria (e.g., Novosphingobium aromaticivorans , [43]) and it is likely that AOX entered eukaryotic lineages via the ancient proteobacterial endosymbiont that gave rise to mitochondria [39]. AOX is also found sporadically in protists and fungi, in many cases within pathogenic organisms within these groups [44,45], but also within important non-pathogenic model systems such as the fungi Neurospora crassa [46] and Podospora anserina [47] Surprisingly, AOX is also present in many animal phyla, although clearly absent from vertebrates and arthropods [39,48]. The finding of AOX in the animal kingdom has spawned several recent studies in which the protein has been introduced into different vertebrates, as a means to study aspects of mitochondrial bioenergetics and signaling [49–51].…”