Pancreatic beta cells lack a low glucose and O2-inducible mitochondrial protein that augments cell survival.
beta cell failure is a common denominator of diabetes. Susceptibility to stress-induced apoptosis may underlie beta cell failure and/or hamper islet transplantation therapy. The causal basis is not well understood. In efforts to identify important differences in gene expression in alpha vs. beta cells, a gene termed HIMP1 (Hypoglycemia/hypoxia Inducible Mitochondrial Protein, or HIG1) has been cloned from an alpha cell cDNA library. It is a member of a well conserved eukaryote protein family. In mice, its two alternatively spliced products each form a transmembrane loop, having an N(outside)-C(outside) orientation and are expressed highly in the mitochondrial inner membrane in several tissues including heart and pancreatic alpha cells, but not in beta cells. Ectopic expression of HIMP1 in MIN6 beta cells protects the cells from apoptosis induced by several stimuli and prolongs their survival. These results suggest an important role for HIMP1 in stress protective programs in mitochondria.
Wang
Jie
J
Department of Biochemistry and Molecular Biology, University of Chicago, and The Howard Hughes Medical Institute, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Cao
Yun
Y
Chen
Ying
Y
Chen
Yimei
Y
Gardner
Paul
P
Steiner
Donald F
DF
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010100:Oxygen / Q000502:physiology*
C512983:Hig1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D005947:Glucose; D010100:Oxygen