SUMMARY PARAGRAPH for SSQ1
SSC1, SSQ1, and ECM10 encode chaperone proteins of the HSP70 family that localize to the mitochondria (5 and reviewed in 6). In addition to these three mitochondrial HSP70s, S. cerevisiae cells also synthesize nine cytosolic HSPs (encoded by SSA1, SSA2, SSA3, SSA4, SSB1, SSB2, SSE1, SSE2, SSZ1) and two that are found in the ER (KAR2, LHS1). HSP70 is a large family of proteins that has been evolutionarily conserved from bacteria (DnaK) to humans (HSP72/73). HSP70 proteins were originally classified based upon their induction by heat shock and their size of ~70kDa. The main function of these proteins is to serve as molecular chaperones, binding unfolded peptides to assist in proper folding and prevent aggregation/misfolding (reviewed in 7 and 8). HSP70s are also involved in disassembling aggregates of misfolded proteins, translocating select proteins into the mitochondria and ER, and degrading aberrant proteins (reviewed in 9, 8, and 7).
Like all other Hsp70 proteins, Ssq1p contains an N-terminal ATPase domain and a C-terminal peptide-binding domain, and binds to unfolded peptides in an ATP-regulated manner (3, 10). The ATPase activity of Ssq1p is cooperatively stimulated by the DnaJ/HSP40 co-chaperone Jac1p and the Fe/S cluster scaffolding protein Isu1p (11). Subsequent ADP-ATP exchange is promoted by the nucleotide exchange factor Mge1p (10). Ssq1p is responsible for mediating the assembly/maturation of mitochondrial proteins containing iron-sulfur (Fe/S) clusters (1, 11). In particular, Ssq1p has been shown to process the maturation of Yfh1p, the yeast homolog of the human protein frataxin, which is involved in the neurodegenerative disease Friedreich's ataxia (OMIM; 2, 12). Loss of Ssq1p results in increased cellular iron uptake, accumulation of mitochondrial iron, cold-sensitivity, and a decrease in enzyme activity of mitochondrial proteins containing an Fe/S center (1, 2, 3).
Last updated: 2006-02-09