MitoNEET is an iron-containing outer mitochondrial membrane protein that regulates oxidative capacity.
Members of the thiazolidinedione (TZD) class of insulin-sensitizing drugs are extensively used in the treatment of type 2 diabetes. Pioglitazone, a member of the TZD family, has been shown to bind specifically to a protein named mitoNEET [Colca JR, McDonald WG, Waldon DJ, Leone JW, Lull JM, Bannow CA, Lund ET, Mathews WR (2004) Am J Physiol 286:E252-E260]. Bioinformatic analysis reveals that mitoNEET is a member of a small family of proteins containing a domain annotated as a CDGSH-type zinc finger. Although annotated as a zinc finger protein, mitoNEET contains no zinc, but instead contains 1.6 mol of Fe per mole of protein. The conserved sequence C-X-C-X(2)-(S/T)-X(3)-P-X-C-D-G-(S/A/T)-H is a defining feature of this unique family of proteins and is likely involved in iron binding. Localization studies demonstrate that mitoNEET is an integral protein present in the outer mitochondrial membrane. An amino-terminal anchor sequence tethers the protein to the outer membrane with the CDGSH domain oriented toward the cytoplasm. Cardiac mitochondria isolated from mitoNEET-null mice demonstrate a reduced oxidative capacity, suggesting that mito- NEET is an important iron-containing protein involved in the control of maximal mitochondrial respiratory rates.
Wiley
Sandra E
SE
Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA.
Murphy
Anne N
AN
Ross
Stuart A
SA
van der Geer
Peter
P
Dixon
Jack E
JE
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid
C525595:CISD1 protein, human; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C519501:mitoNEET protein, mouse; C481940:mitochondrial protein 17 kDa, rat; D007501:Iron; D010100:Oxygen