Oxidative phosphorylation provides stress resistance in quiescent cells
Author(s)
Rohlena, Jakub
Novais, Silvia Magalhaes
Blecha, Jan
Rohlenova, Katerina
Neuzil, Jiri
Griffith University Author(s)
Year published
2019
Metadata
Show full item recordAbstract
Mitochondrial oxidative phosphorylation system (OXPHOS) is recognized as a producer of ATP. In proliferating cells, OXPHOS also fulfills important ATP‐unrelated functions, such as production of pyrimidines in the de‐novo biosynthetic pathway needed to sustain high rates of proliferation. In contrast, no such requirement for pyrimidines exists in cells that are not proliferating, and additional ATP‐unrelated functions of OXPHOS are poorly defined in this situation. For this reason, we produced mitochondrial DNA (mtDNA)‐depleted ρ0 cells capable of contact inhibition and discovered that in the contact‐inhibited state these ...
View more >Mitochondrial oxidative phosphorylation system (OXPHOS) is recognized as a producer of ATP. In proliferating cells, OXPHOS also fulfills important ATP‐unrelated functions, such as production of pyrimidines in the de‐novo biosynthetic pathway needed to sustain high rates of proliferation. In contrast, no such requirement for pyrimidines exists in cells that are not proliferating, and additional ATP‐unrelated functions of OXPHOS are poorly defined in this situation. For this reason, we produced mitochondrial DNA (mtDNA)‐depleted ρ0 cells capable of contact inhibition and discovered that in the contact‐inhibited state these cells are much more sensitive to an oxidative insult than the parental cells with normal bioenergetics. Unlike parental cells, quiescent ρ0 cells featured suppressed autophagy, and pharmacological or genetic interference with the autophagy pathway in the parental cells phenocopied effects of OXPHOS deficiency on susceptibility to oxidative stress. While the precise mechanism of autophagy suppression in OXPHOS‐deficient quiescent cells is under investigation, we conclude that a distinct aspect of OXPHOS function in quiescence is to provide stress resistance through maintenance of autophagy.
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View more >Mitochondrial oxidative phosphorylation system (OXPHOS) is recognized as a producer of ATP. In proliferating cells, OXPHOS also fulfills important ATP‐unrelated functions, such as production of pyrimidines in the de‐novo biosynthetic pathway needed to sustain high rates of proliferation. In contrast, no such requirement for pyrimidines exists in cells that are not proliferating, and additional ATP‐unrelated functions of OXPHOS are poorly defined in this situation. For this reason, we produced mitochondrial DNA (mtDNA)‐depleted ρ0 cells capable of contact inhibition and discovered that in the contact‐inhibited state these cells are much more sensitive to an oxidative insult than the parental cells with normal bioenergetics. Unlike parental cells, quiescent ρ0 cells featured suppressed autophagy, and pharmacological or genetic interference with the autophagy pathway in the parental cells phenocopied effects of OXPHOS deficiency on susceptibility to oxidative stress. While the precise mechanism of autophagy suppression in OXPHOS‐deficient quiescent cells is under investigation, we conclude that a distinct aspect of OXPHOS function in quiescence is to provide stress resistance through maintenance of autophagy.
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Conference Title
European Journal of Clinical Investigation
Volume
49
Issue
S1
Subject
Clinical sciences
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
Medicine, Research & Experimental
General & Internal Medicine