title: Mitochondria, cholesterol and cancer cell metabolism.
abstract: Given the role of mitochondria in oxygen consumption, metabolism and cell death regulation, alterations in mitochondrial function or dysregulation of cell death pathways contribute to the genesis and progression of cancer. Cancer cells exhibit an array of metabolic transformations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which ensure cancer progression. Cholesterol metabolism is disturbed in cancer cells and supports uncontrolled cell growth. In particular, the accumulation of cholesterol in mitochondria emerges as a molecular component that orchestrates some of these metabolic alterations in cancer cells by impairing mitochondrial function. As a consequence, mitochondrial cholesterol loading in cancer cells may contribute, in part, to the Warburg effect stimulating aerobic glycolysis to meet the energetic demand of proliferating cells, while protecting cancer cells against mitochondrial apoptosis due to changes in mitochondrial membrane dynamics. Further understanding the complexity in the metabolic alterations of cancer cells, mediated largely through alterations in mitochondrial function, may pave the way to identify more efficient strategies for cancer treatment involving the use of small molecules targeting mitochondria, cholesterol homeostasis/trafficking and specific metabolic pathways.
authors.affiliation: Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Consejo Superior Investigaciones Cientificas (CSIC), Barcelona, Spain.|Liver Unit-Hospital Clínic, Centre Esther Koplowitz, IDIBAPS, CIBEREHD, Planta Cuarta, C/Rosselló 149, Barcelona, 08036, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Ribas
authors.affiliation: Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Consejo Superior Investigaciones Cientificas (CSIC), Barcelona, Spain.|Liver Unit-Hospital Clínic, Centre Esther Koplowitz, IDIBAPS, CIBEREHD, Planta Cuarta, C/Rosselló 149, Barcelona, 08036, Spain.|Research Center for ALPD and Cirrhosis, Ckeck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Ruiz
authors.affiliation: Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Consejo Superior Investigaciones Cientificas (CSIC), Barcelona, Spain. Checa229@yahoo.com.|Liver Unit-Hospital Clínic, Centre Esther Koplowitz, IDIBAPS, CIBEREHD, Planta Cuarta, C/Rosselló 149, Barcelona, 08036, Spain. Checa229@yahoo.com.|Research Center for ALPD and Cirrhosis, Ckeck School of Medicine, University of Southern California, Los Angeles, CA, USA. Checa229@yahoo.com.
authors.forename: José C
authors.initials: JC
authors.lastname: Fernández-Checa
keywords: Apoptosis; Cholesterol; Mitochondria; Reactive oxygen species; Tumor metabolism; Warburg effect