TY - JOUR
T1 - Haeme-regulated degradation of δ-aminolevulinate synthase 1 in rat liver mitochondria
AU - Yoshino, Kazuhisa
AU - Munakata, Hiroshi
AU - Kuge, Osamu
AU - Ito, Akio
AU - Ogishima, Tadashi
N1 - Funding Information:
We thank Prof. Kenji Yamamoto and Prof. Hideyuki Yamada for valuable advice, and Prof. Katsuyoshi Mihara for providing anti-TOM40 antibody. This work was supported by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/10
Y1 - 2007/10
N2 - Protein turnover, which occurs at various rates, is critical for the homeostasis of cellular protein levels. However, the proteolysis systems that determine the turnover rate of mitochondrial proteins are largely unknown. Delta-aminolevulinic acid synthase (ALAS) 1, a rate-limiting enzyme in the haeme biosynthesis, is one of the mitochondrial proteins that have a very short lifetime. In this study, to reveal the regulatory mechanisms for ALAS1 degradation, we examined the turnover rates of ALAS1 in rat liver under several conditions. In primary rat hepatocytes, the degradation of ALAS1 was stimulated by haeme, and suppressed by inhibition of haeme biosynthesis. Furthermore, the haeme-stimulated degradation of ALAS1 was observed in the isolated mitochondria. These results suggested that, in mitochondria, there exists an ALAS1 degradation system that is regulated by cellular haeme level and plays a crucial role in the regulation of haeme biosynthesis.
AB - Protein turnover, which occurs at various rates, is critical for the homeostasis of cellular protein levels. However, the proteolysis systems that determine the turnover rate of mitochondrial proteins are largely unknown. Delta-aminolevulinic acid synthase (ALAS) 1, a rate-limiting enzyme in the haeme biosynthesis, is one of the mitochondrial proteins that have a very short lifetime. In this study, to reveal the regulatory mechanisms for ALAS1 degradation, we examined the turnover rates of ALAS1 in rat liver under several conditions. In primary rat hepatocytes, the degradation of ALAS1 was stimulated by haeme, and suppressed by inhibition of haeme biosynthesis. Furthermore, the haeme-stimulated degradation of ALAS1 was observed in the isolated mitochondria. These results suggested that, in mitochondria, there exists an ALAS1 degradation system that is regulated by cellular haeme level and plays a crucial role in the regulation of haeme biosynthesis.
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U2 - 10.1093/jb/mvm159
DO - 10.1093/jb/mvm159
M3 - Article
C2 - 17761694
AN - SCOPUS:38449083833
SN - 0021-924X
VL - 142
SP - 453
EP - 458
JO - Journal of biochemistry
JF - Journal of biochemistry
IS - 4
ER -