Characterization of a novel chaperone-system in the mitochondrial intermembrane space.

Mitochondria are composed of ~1100 proteins of which more than 99% are imported. Proteins are imported in an unfolded manner through pores in the outer and inner mitochondrial membrane (TOMs and TIMMs, respectively). Once imported, the unfolded peptides must be refolded into their native conformation. This requires a dedicated protein quality control system in each of the different mitochondrial compartments. To this end, the mitochondrial matrix contains a specific set of molecular chaperones (like mtHSP60 and mtHSP70). However, classical chaperones like Hsp70 and Hsp90 have not been identified in the mitochondrial intermembrane space (IMS). So how proteins are folded in the IMS remains incompletely understood. The mitochondrial IMS developed from the bacterial periplasm and, since the periplasm is devoid of ATP, the periplasm was shown to contain a number of ATP-independent chaperones such as Skp, Spy and HdeA. This suggests that mammalians might possess equivalent chaperones in the IMS. Indeed, we have identified a new class of chaperones that are also ATP-independent and which reside in the mitochondrial IMS. In this proposal we aim to elucidate how this new chaperone system contributes to the mitochondrial proteostasis.

Keywords:MITOCHONDRIA, CHARCOT-MARIE-TOOTH DISEASE

Disciplines:Molecular and cell biology not elsewhere classified

Project type:Collaboration project