Mitochondria: a target for cancer therapy.
Mitochondria, the cells powerhouses, are essential for maintaining cell life, and they also play a major role in regulating cell death, which occurs upon permeabilization of their membranes. Once mitochondrial membrane permeabilization (MMP) occurs, cells die either by apoptosis or necrosis. Key factors regulating MMP include calcium, the cellular redox status (including levels of reactive oxygen species) and the mobilization and targeting to mitochondria of Bcl-2 family members. Contemporary approaches to targeting mitochondria in cancer therapy use strategies that either modulate the action of Bcl-2 family members at the mitochondrial outer membrane or use specific agents that target the mitochondrial inner membrane and the mitochondrial permeability transition (PT) pore. The aim of this review is to describe the major mechanisms regulating MMP and to discuss, with examples, mitochondrial targeting strategies for potential use in cancer therapy.
Armstrong
Jeffrey S
JS
Department of Biochemistry, Faculty of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore. bchjsa@nus.edu.sg
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000502:physiology; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D010455:Peptides / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000502:physiology; D014862:Wasp Venoms / Q000494:pharmacology
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D036341:Intercellular Signaling Peptides and Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D014862:Wasp Venoms; C037500:mastoparan; D016572:Cyclosporine; D045304:Cytochromes c