Mitochondrial protein phosphorylation: instigator or target of lipotoxicity?
Lipotoxicity occurs as a consequence of chronic exposure of non-adipose tissue and cells to elevated concentrations of fatty acids, triglycerides and/or cholesterol. The contribution of mitochondria to lipotoxic cell dysfunction, damage and death is associated with elevated production of reactive oxygen species and initiation of apoptosis. Although there is a broad consensus on the involvement of these phenomena with lipotoxicity, the molecular mechanisms that initiate, mediate and trigger mitochondrial dysfunction in response to substrate overload remain unclear. Here, we focus on protein phosphorylation as an important phenomenon in lipotoxicity that harms mitochondria-related signal transduction and integration in cellular metabolism. Moreover, the degradation of mitochondria by mitophagy is discussed as an important landmark that leads to cellular apoptosis in lipotoxicity.
Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University Graz, Graz, Austria. wolfgang.graier@medunigraz.at
Wolfgang F
WF
Graier
Roland
R
Malli
Gerhard M
GM
Kostner
D000818:Animals; D017209:Apoptosis; D004041:Dietary Fats / Q000009:adverse effects; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology
D004041:Dietary Fats; D024101:Mitochondrial Proteins