Prohibitin and mitochondrial biology

Prohibitins are ubiquitous, evolutionarily conserved proteins that are mainly localized in mitochondria. The mitochondrial prohibitin complex comprises two subunits, PHB1 and PHB2. These two proteins assemble into a ring-like macromolecular structure at the inner mitochondrial membrane and are implicated in diverse cellular processes: from mitochondrial biogenesis and function to cell death and replicative senescence. In humans, prohibitins have been associated with various types of cancer. While their biochemical function remains poorly understood, studies in organisms ranging from yeast to mammals have provided significant insights into the role of the prohibitin complex in mitochondrial biogenesis and metabolism. Here we review recent studies and discuss their implications for deciphering the function of prohibitins in mitochondria. Prohibitins are ubiquitous, evolutionarily conserved proteins that are mainly localized in mitochondria. The mitochondrial prohibitin complex comprises two subunits, PHB1 and PHB2. These two proteins assemble into a ring-like macromolecular structure at the inner mitochondrial membrane and are implicated in diverse cellular processes: from mitochondrial biogenesis and function to cell death and replicative senescence. In humans, prohibitins have been associated with various types of cancer. While their biochemical function remains poorly understood, studies in organisms ranging from yeast to mammals have provided significant insights into the role of the prohibitin complex in mitochondrial biogenesis and metabolism. Here we review recent studies and discuss their implications for deciphering the function of prohibitins in mitochondria. the time that non-dividing yeast cells remain viable in a stationary phase culture. S. cerevisiae switch metabolism from fermentation to respiration when growing on glucose and in the presence of oxygen. During the first growth phase, when there is plenty of glucose and oxygen available, yeast cells prefer glucose fermentation to aerobic respiration. After glucose is depleted, yeast cells undergo a metabolic (or diauxic) shift, where the fermentative product ethanol is oxidised. This diauxic shift is accompanied by stimulation of mitochondrial function. an inherited neurological disorder characterized by retrograde degeneration of cortical motor axons, progressive weakness (paraplegia), increased muscle tone and stiffness (spasticity) of the legs. Loss of function of paraplegin (encoded by the gene SPG7, a mitochondrial m-AAA-protease) causes HSP. immunoglobulin M. An antibody that is present on B lymphocytes that are involved in the humoral immune response. IgM is the primary antibody against A and B antigens on red blood cells. a neurodegenerative disorder of infancy or childhood, generally due to mutations in nuclear or mitochondrial genes involved in mitochondrial energy metabolism. mitochondrial matrix-AAA protease. Member of membrane-bound ATP-dependent proteases that are present in eubacteria, mitochondria and chloroplasts and that can degrade membrane proteins. discrete protein-DNA complexes, organizing multiple mitochondrial DNA (mtDNA) molecules. the yeast S. cerevisiae can grow in the absence of mtDNA. Yeast strains that contain wild-type mtDNA, called [rho+] cells, can respire and grow on non-fermentable carbon sources. Cells that contain deletions or mutations in mtDNA [rho-] or have completely lost their mtDNA [rho0] are called petite mutants. Petite mutants can grow by fermentation in glucose media. Petite-negative yeast species lose viability in fermentable carbon sources. yeast cells age chronologically but also undergo replicative senescence. The replicative lifespan reflects the number of buds generated by an individual mother cell. the ability of yeast cells to grow on non-fermentable carbon sources, where respiration (aerobic growth) is required. deletions of the mitochondrial genome that render yeast cells respiration-deficient (petite phenotype – see above). when nutrients are exhausted, yeast cells enter a stationary phase that is characterized by cell cycle arrest (G0) and specific physiological, biochemical, and morphological changes.