TY - JOUR
T1 - Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence
AU - Coates, P.J.
AU - Nenutil, R.
AU - McGregor, A.
AU - Picksley, S.M.
AU - Crouch, D.H.
AU - Hall, P.A.
AU - Wright, E.G.
N1 - Medline is the source for the MeSH terms of this document.
PY - 2001/5/1
Y1 - 2001/5/1
N2 - The two prohibitin proteins, Phblp and Phb2pBAB37, have been ascribed various functions, including cell cycle regulation, apoptosis, assembly of mitochondrial respiratory chain enzymes, and aging. We show that the mammalian prohibitins are present in the inner mitochondrial membrane and are always bound to each other, with no free protein detectable. They are coexpressed during development and in adult mammalian tissues, and expression levels are indicative of a role in mitochondrial metabolism, but are not compatible with roles in the regulation of cellular proliferation or apoptosis. High level expression of the proteins is consistently seen in primary human tumors, while cellular senescence of human and chick fibroblasts is accompanied by heterogeneous decreases in both proteins. The two proteins are induced by metabolic stress caused by an imbalance in the synthesis of mitochondrial- and nuclear-encoded mitochondrial proteins, but do not respond to oxidative stress, heat shock, or other cellular stresses. The gene promoter sequences contain binding sites for the Myc oncoprotein and overexpression of Myc induces expression of the prohibitins. The data support conserved roles for the prohibitins in regulating mitochondrial respiratory activity and in aging.
AB - The two prohibitin proteins, Phblp and Phb2pBAB37, have been ascribed various functions, including cell cycle regulation, apoptosis, assembly of mitochondrial respiratory chain enzymes, and aging. We show that the mammalian prohibitins are present in the inner mitochondrial membrane and are always bound to each other, with no free protein detectable. They are coexpressed during development and in adult mammalian tissues, and expression levels are indicative of a role in mitochondrial metabolism, but are not compatible with roles in the regulation of cellular proliferation or apoptosis. High level expression of the proteins is consistently seen in primary human tumors, while cellular senescence of human and chick fibroblasts is accompanied by heterogeneous decreases in both proteins. The two proteins are induced by metabolic stress caused by an imbalance in the synthesis of mitochondrial- and nuclear-encoded mitochondrial proteins, but do not respond to oxidative stress, heat shock, or other cellular stresses. The gene promoter sequences contain binding sites for the Myc oncoprotein and overexpression of Myc induces expression of the prohibitins. The data support conserved roles for the prohibitins in regulating mitochondrial respiratory activity and in aging.
UR - http://www.scopus.com/inward/record.url?scp=0035325241&partnerID=8YFLogxK
U2 - 10.1006/excr.2001.5166
DO - 10.1006/excr.2001.5166
M3 - Article
C2 - 11302691
AN - SCOPUS:0035325241
SN - 0014-4827
VL - 265
SP - 262
EP - 273
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -