TY - JOUR
T1 - Mitochondrial involvement in non-alcoholic steatohepatitis
AU - Serviddio, Gaetano
AU - Sastre, Juan
AU - Bellanti, Francesco
AU - Viña, José
AU - Vendemiale, Gianluigi
AU - Altomare, Emanuele
PY - 2008/2
Y1 - 2008/2
N2 - Non-alcoholic steatohepatitis (NASH) is an increasing recognized condition that may progress to end-stage liver disease. There are consistent evidences that mitochondrial dysfunction plays a central role in NASH whatever its origin. Mitochondria are the key controller of fatty acids removal and this is part of an intensive gene program that modifies hepatocytes to counteract the excessive fat storage. Mitochondrial dysfunction participates at different levels in NASH pathogenesis since it impairs fatty liver homeostasis and induces overproduction of ROS that in turn trigger lipid peroxidation, cytokines release and cell death. In this review we briefly recall the role of mitochondria in fat metabolism and energy homeostasis and focus on the role of mitochondrial impairment and uncoupling proteins in the pathophysiology of NASH progression. We suggest that mitochondrial respiratory chain, UCP2 and redox balance cooperate in a common pathway that permits to set down the mitochondrial redox pressure, limits the risk of oxidative damage, and allows the maximal rate of fat removal. When the environmental conditions change and high energy supply occurs, hepatocytes are unable to replace their ATP store and steatosis progress to NASH and cirrhosis. The beneficial effects of some drugs on mitochondrial function are also discussed.
AB - Non-alcoholic steatohepatitis (NASH) is an increasing recognized condition that may progress to end-stage liver disease. There are consistent evidences that mitochondrial dysfunction plays a central role in NASH whatever its origin. Mitochondria are the key controller of fatty acids removal and this is part of an intensive gene program that modifies hepatocytes to counteract the excessive fat storage. Mitochondrial dysfunction participates at different levels in NASH pathogenesis since it impairs fatty liver homeostasis and induces overproduction of ROS that in turn trigger lipid peroxidation, cytokines release and cell death. In this review we briefly recall the role of mitochondria in fat metabolism and energy homeostasis and focus on the role of mitochondrial impairment and uncoupling proteins in the pathophysiology of NASH progression. We suggest that mitochondrial respiratory chain, UCP2 and redox balance cooperate in a common pathway that permits to set down the mitochondrial redox pressure, limits the risk of oxidative damage, and allows the maximal rate of fat removal. When the environmental conditions change and high energy supply occurs, hepatocytes are unable to replace their ATP store and steatosis progress to NASH and cirrhosis. The beneficial effects of some drugs on mitochondrial function are also discussed.
KW - ATP homeostasis
KW - Fatty liver
KW - HNE
KW - Mitochondria
KW - NASH
KW - Reactive oxygen species
KW - UCP2
UR - http://www.scopus.com/inward/record.url?scp=39749127250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39749127250&partnerID=8YFLogxK
U2 - 10.1016/j.mam.2007.09.014
DO - 10.1016/j.mam.2007.09.014
M3 - Article
C2 - 18061659
AN - SCOPUS:39749127250
VL - 29
SP - 22
EP - 35
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
SN - 0098-2997
IS - 1-2
ER -