A novel role of peroxin PEX6: suppression of aging defects in mitochondria.
Yeast cells become older with each division, but their daughters are born young. Mutational analysis shows that maintenance of this age asymmetry requires segregation of a complement of active mitochondria to daughters and that this process breaks down in older mother cells. This decline has implications for stem cell aging in higher organisms. PEX6, a peroxisome biogenesis gene, has been isolated as a multicopy suppressor of an atp2 age asymmetry mutant. Suppression depended on the presence of particular amino acid residues in Atp2p, and required adenosine triphosphate (ATP) binding and/or ATP hydrolysis activity of Pex6p. Extra copies of PEX6 corrected the deficit in Atp2p in mitochondria in the mutant by improving its import kinetics, resulting in near normal mitochondrial inheritance by daughter cells. The novel function of Pex6p described here may provide insights into peroxisomal and mitochondrial disorders and into metabolic diseases in general.
Seo
Jae-Gu
JG
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Lai
Chi-Yung
CY
Miceli
Michael V
MV
Jazwinski
S Michal
SM
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging; D016922:Cellular Senescence; D003600:Cytosol / Q000378:metabolism; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D020675:Peroxisomes / Q000378:metabolism; D020161:Physical Chromosome Mapping; D010957:Plasmids / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases; D000074183:ATPases Associated with Diverse Cellular Activities; C490760:PEX6 protein, S cerevisiae; C471230:ATP2 protein, S cerevisiae