TY - JOUR
T1 - Mitochondrial morphology and dynamics in hepatocytes from normal and ethanol-fed rats
AU - Das, Sudipto
AU - Hajnóczky, Nora
AU - Antony, Anil Noronha
AU - Csordás, György
AU - Gaspers, Lawrence D.
AU - Clemens, Dahn L.
AU - Hoek, Jan B.
AU - Hajnóczky, György
N1 - Funding Information:
The assistance of Mr. David Weaver with confocal microscopy is greatly appreciated. This work was supported by NIH grants AA017773 to J.B.H. and G.H. and AA017752 to L.D.G.
PY - 2012/7
Y1 - 2012/7
N2 - Mitochondrial structure and function are central to cell physiology and are mutually interdependent. Mitochondria represent a primary target of the alcohol-induced tissue injury, particularly in the liver, where the metabolic effects of ethanol are predominant. However, the effect of ethanol on hepatic mitochondrial morphology and dynamics remain to be established. In the present work, we employed the organelle-targeted photoactivatable fluorescent protein technology and electron microscopy to study hepatic mitochondrial structure and dynamics. Hepatocytes in perfused liver as well as in primary cultures showed mostly discrete globular or short tubular mitochondria. The mitochondria showed few fusion events and little movement activity. By contrast, human hepatoma (HepG2)-derived VL-17A cells, expressing the major hepatic ethanol metabolizing enzymes, alcohol dehydrogenase and cytochrome P450 2E1, have elongated and interconnected mitochondria showing matrix continuity and many fusion events. Hepatocytes isolated from chronically ethanol-fed rats showed some increase in mitochondrial volume and exhibited a substantial suppression of mitochondrial dynamics. In VL-17A cells, prolonged ethanol exposure also caused decreased mitochondrial continuity and dynamics. Collectively, these results indicate that mitochondria in normal hepatocytes show relatively slow dynamics, which is very sensitive to suppression by ethanol exposure.
AB - Mitochondrial structure and function are central to cell physiology and are mutually interdependent. Mitochondria represent a primary target of the alcohol-induced tissue injury, particularly in the liver, where the metabolic effects of ethanol are predominant. However, the effect of ethanol on hepatic mitochondrial morphology and dynamics remain to be established. In the present work, we employed the organelle-targeted photoactivatable fluorescent protein technology and electron microscopy to study hepatic mitochondrial structure and dynamics. Hepatocytes in perfused liver as well as in primary cultures showed mostly discrete globular or short tubular mitochondria. The mitochondria showed few fusion events and little movement activity. By contrast, human hepatoma (HepG2)-derived VL-17A cells, expressing the major hepatic ethanol metabolizing enzymes, alcohol dehydrogenase and cytochrome P450 2E1, have elongated and interconnected mitochondria showing matrix continuity and many fusion events. Hepatocytes isolated from chronically ethanol-fed rats showed some increase in mitochondrial volume and exhibited a substantial suppression of mitochondrial dynamics. In VL-17A cells, prolonged ethanol exposure also caused decreased mitochondrial continuity and dynamics. Collectively, these results indicate that mitochondria in normal hepatocytes show relatively slow dynamics, which is very sensitive to suppression by ethanol exposure.
KW - Alcohol
KW - Alcoholic liver disease
KW - Fusion
KW - Mitochondria
KW - Motility
KW - Oxidative stress
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U2 - 10.1007/s00424-012-1100-4
DO - 10.1007/s00424-012-1100-4
M3 - Article
C2 - 22526459
AN - SCOPUS:84863528013
VL - 464
SP - 101
EP - 109
JO - Pflugers Archiv fur die gesamte Physiologie des Menschen und der Tiere
JF - Pflugers Archiv fur die gesamte Physiologie des Menschen und der Tiere
SN - 0031-6768
IS - 1
ER -