What is the functional significance of the unique location of glutaredoxin 1 (GRx1) in the intermembrane space of mitochondria?
Glutaredoxins (GRx) catalyze reversible protein glutathionylation. They are implicated in sulfhydryl homeostasis and regulation of redox signal transduction, controlling various cellular processes like DNA synthesis, defense against oxidative stress, apoptosis signaling, and DNA-binding of transcription factors. Two isoforms of GRx are well characterized in mammals: GRx1, the "cytosolic" form, and GRx2, the "mitochondrial" form. Here we report documentation of GRx1 in mitochondria, localized exclusively in the intermembrane space and segregated from GRx2, localized exclusively in the mitochondrial matrix. We hypothesize that GRx1 and GRx2 in their unique locations regulate different functions of the mitochondria via reversible S-glutathionylation.
Pai
Harish V
HV
Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio.
Starke
David W
DW
Lesnefsky
Edward J
EJ
Hoppel
Charles L
CL
Mieyal
John J
JJ
D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D054477:Glutaredoxins / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000737:chemistry* / Q000201:enzymology; D008930:Mitochondria, Liver / Q000737:chemistry* / Q000201:enzymology; D051336:Mitochondrial Membranes / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; C516007:Glrx protein, rat; D054477:Glutaredoxins; D020033:Protein Isoforms; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase