Sorting of D-lactate dehydrogenase to the inner membrane of mitochondria. Analysis of topogenic signal and energetic requirements

J Biol Chem. 1998 Apr 3;273(14):8040-7. doi: 10.1074/jbc.273.14.8040.

Abstract

D-Lactate dehydrogenase (D-LD) is located in the inner membrane of mitochondria. It spans the membrane once in an Nin-Cout orientation with the bulk of the protein residing as a folded domain in the intermembrane space. D-LD is synthesized as a precursor with an N-terminal cleavable presequence and is imported into the mitochondria in a Deltapsi-dependent, but mt-Hsp70-independent manner. Upon import in vitro D-LD folds in the intermembrane space to attain a conformation indistinguishable from endogenous D-LD. Sorting of D-LD to the inner membrane is directed by a composite topogenic signal consisting of the hydrophobic transmembrane segment and a cluster of charged amino acids C-terminal to it. We propose a model for the mode of operation of the sorting signal of D-LD. This model also accounts for the driving force of translocation across the outer membrane, in the apparent absence of mt-Hsp70-dependent assisted import and involves the folding of the D-LD in the intermembrane space.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism
  • Energy Metabolism
  • L-Lactate Dehydrogenase / chemistry
  • L-Lactate Dehydrogenase / metabolism*
  • Lactate Dehydrogenases*
  • Mitochondria / enzymology*
  • Protein Folding
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / ultrastructure

Substances

  • Lactate Dehydrogenases
  • L-Lactate Dehydrogenase
  • D-lactate dehydrogenase