title: Sorting of D-lactate dehydrogenase to the inner membrane of mitochondria. Analysis of topogenic signal and energetic requirements.
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.
authors.affiliation: Institut für Physiologische Chemie, Geethestrasse 33, 80336 München, Germany.
authors.forename: E E
authors.initials: EE
authors.lastname: Rojo
authors.forename: B
authors.initials: B
authors.lastname: Guiard
authors.forename: W
authors.initials: W
authors.lastname: Neupert
authors.forename: R A
authors.initials: RA
authors.lastname: Stuart
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D004734:Energy Metabolism; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D045022:Lactate Dehydrogenases; D008928:Mitochondria / Q000201:enzymology*; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000648:ultrastructure
chemical_list: D045022:Lactate Dehydrogenases; D007770:L-Lactate Dehydrogenase; C071195:D-lactate dehydrogenase