The forkhead transcription factor Hcm1 promotes mitochondrial biogenesis and stress resistance in yeast.
In Saccharomyces cerevisiae, the forkhead transcription factor Hcm1 is involved in chromosome segregation, spindle pole dynamics, and budding. We found that Hcm1 interacts with the histone deacetylase Sir2 and shifts from cytoplasm to the nucleus in the G(1)/S phase or in response to oxidative stress stimuli. The nuclear localization of Hcm1 depends on the activity of Sir2 as revealed by activators and inhibitors of the sirtuins and the Δsir2 mutant. Hcm1-overexpressing cells display more mitochondria that can be attributed to increased amounts of Abf2, a protein involved in mitochondrial biogenesis. These cells also show higher rates of oxygen consumption and improved resistance to oxidative stress that would be explained by increased catalase and Sod2 activities and molecular chaperones such as Hsp26, Hsp30, and members of Hsp70 family. Microarray analyses also reveal increased expression of genes involved in mitochondrial energy pathways and those allowing the transition from the exponential to the stationary phase. Taken together, these results describe a new and relevant role of Hcm1 for mitochondrial functions, suggesting that this transcription factor would participate in the adaptation of cells from fermentative to respiratory metabolism.
Rodriguez-Colman
Maria José
MJ
Biochemistry of Oxidative Stress Group, IRBLleida, University of Lleida, 25008 Lleida, Spain.
Reverter-Branchat
Gemma
G
Sorolla
M Alba
MA
Tamarit
Jordi
J
Ros
Joaquim
J
Cabiscol
Elisa
E
D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D050890:HSP30 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D010101:Oxygen Consumption; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D056565:Sirtuin 2 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D015415:Biomarkers; D002374:Catalase; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D050890:HSP30 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056565:Sirtuin 2; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C072843:ABF2 protein, S cerevisiae; C079874:HCM1 protein, S cerevisiae; C499528:HSP26 protein, S cerevisiae; C494390:HSP30 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae