TY - JOUR
T1 - Excess membrane cholesterol is not responsible for metabolic and bioenergetic changes in AS-30D hepatoma mitochondria
AU - Dietzen, Dennis J.
AU - Davis, E. Jack
PY - 1994/3
Y1 - 1994/3
N2 - Using mitochondria isolated from normal rat liver and AS-30D hepatoma in addition to cholesterol-enriched mitochondria, we have evaluated the ability of membrane cholesterol to induce changes in mitochondrial function, specifically, the preferential export of citrate (i.e., truncation of the Krebs cycle). Two in vitro cholesterol-enrichment procedures failed to produce mitochondria with any physiologically significant increases in free membrane cholesterol. Alternatively, male Wistar rats were maintained on a 2% cholesterol diet to elevate mitochondrial cholesterol. This treatment resulted in liver mitochondria which contained 70% of the cholesterol levels found in AS-30D hepatoma mitochondria, yet only minor metabolic and bioenergetic alterations. Subfractionation of the various mitochondrial preparations revealed that cholesterol was located primarily in outer membranes of both the cholesterol-enriched and AS-30D preparations. We therefore conclude that an increase in membrane cholesterol is not sufficient to induce "truncation" of the citric acid cycle or any other mitochondrial abnormality in tumor cells.
AB - Using mitochondria isolated from normal rat liver and AS-30D hepatoma in addition to cholesterol-enriched mitochondria, we have evaluated the ability of membrane cholesterol to induce changes in mitochondrial function, specifically, the preferential export of citrate (i.e., truncation of the Krebs cycle). Two in vitro cholesterol-enrichment procedures failed to produce mitochondria with any physiologically significant increases in free membrane cholesterol. Alternatively, male Wistar rats were maintained on a 2% cholesterol diet to elevate mitochondrial cholesterol. This treatment resulted in liver mitochondria which contained 70% of the cholesterol levels found in AS-30D hepatoma mitochondria, yet only minor metabolic and bioenergetic alterations. Subfractionation of the various mitochondrial preparations revealed that cholesterol was located primarily in outer membranes of both the cholesterol-enriched and AS-30D preparations. We therefore conclude that an increase in membrane cholesterol is not sufficient to induce "truncation" of the citric acid cycle or any other mitochondrial abnormality in tumor cells.
UR - http://www.scopus.com/inward/record.url?scp=0028318531&partnerID=8YFLogxK
U2 - 10.1006/abbi.1994.1122
DO - 10.1006/abbi.1994.1122
M3 - Article
C2 - 8135546
AN - SCOPUS:0028318531
SN - 0003-9861
VL - 309
SP - 341
EP - 347
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -