Mitochondrial carrier protein biogenesis: role of the chaperones Hsc70 and Hsp90

作者：Zara Vincenzo^*; Ferramosca Alessandra; Robitaille Foucher Philippe; Palmieri Ferdinando; Young Jason C

来源：Biochemical Journal, 2009, 419(2): 369-375.

DOI：10.1042/BJ20082270

• chaperone
• heat-shock cognate 70 (Hsc70)
• heat-shock protein 90 (Hsp90)
• metabolite carrier protein
• mitochondrial import
• translocase of the mitochondrial outer membrane 70 (Tom70)

Metabolite carrier proteins of the mitochondrial inner membrane share homology in their transmembrane domains, which also carries their targeting information. In addition, some carriers have cleavable presequences which are not essential for targeting, but have some other function before import. The cytosolic chaperones Hsc70 (heat-shock cognate 70) and Hsp90 (heat-shock protein 90) complex with carrier precursors and interact specifically with the Toni (translocase of the mitochondrial outer membrane) 70 import receptor to promote import. We analysed how the presequences of the PiC (phosphate carrier) and CIC (citrate carrier) relate to the mechanisms of chaperone-mediated import. Deletion of the PiC presequence reduced the efficiency of import but, notably, not by causing aggregation. Instead, binding of the protein to Hsc70 was reduced, as well as the dependence oil Hsc70 for import. Hsp90 binding and function in import was not greatly affected, but it could not entirely compensate for the lack of Hsc70 interaction. Deletion of the presequence front CIC was shown to cause its aggregation, but had little effect oil the contribution to import of either Hsc70 or Hsp90. The presequence of PiC, but not that of CIC, conferred Hsc70 binding to dihydrofolate reductase fusion proteins. fit comparison, OGC (oxoglutarate carrier) lacks a presequence and was more Soluble, though it is still dependent on both Hsc70 and Hsp90. We propose that carrier presequences evolved to improve targeting competence by different mechanisms, depending oil physical properties of the precursors in the cytosolic targeting environment.

• 出版日期2009-4-15