Protein unfolding by the mitochondrial membrane potential

Area of Science:

• Mitochondrial biology
• Protein import and folding

Background:

• Mitochondria import precursor proteins via N-terminal unraveling.
• The mechanisms inducing this unfolding remain unclear.
• Key candidates for unfolding include the inner mitochondrial membrane potential and matrix-bound Hsp70.

Purpose of the Study:

• To investigate the roles of electrical potential and mitochondrial Hsp70 in precursor protein unfolding during mitochondrial import.

Main Methods:

• The study proposes a model based on the interaction of charged amino acid side chains in targeting sequences with the electrical potential.
• It differentiates conditions under which electrical potential versus Hsp70 mediates unfolding.

Main Results:

• The electrical potential directly unfolds many precursor proteins by acting on positively charged residues in their targeting sequences.
• Mitochondrial Hsp70 unfolds precursor proteins with sufficiently long targeting sequences that reach the matrix.
• Hsp70-mediated unfolding occurs independently of the membrane potential.

Conclusions:

• The inner mitochondrial membrane potential is a primary driver for unfolding many precursor proteins.
• Mitochondrial Hsp70 acts as a secondary unfolding mechanism for specific precursors under distinct conditions.