Mitochondria-Targeted Disruptors and Inhibitors of Cytochrome C/Cardiolipin Peroxidase Complexes: A New Strategy in Anti-Apoptotic Drug Discovery

Details

• Personal Author:
  Atkinson J ; Bayin A ; Bayin H ; Belikova NA ; Borisenko GG ; Chapkin RS ; Greenberger JS ; Kagan VE ; Stoyanovsky D ; Tyurina YY ; Wipf P
• Description:
  The critical role of mitochondria in programmed cell death leads to the design of mitochondriotropic agents as a strategy in regulating apoptosis. For anticancer therapy, stimulation of proapoptotic mitochondrial events in tumor cells and their suppression in surrounding normal cells represents a promising paradigm for new therapies. Different approaches targeting regulation of components of mitochondrial antioxidant system such as Mn-SOD demonstrated significant antitumor efficiency, particularly in combination therapy. This review is focused on a newly discovered early stage of mitochondria-dependent apoptosis - oxidative lipid signaling involving a mitochondria-specific phospholipid cardiolipin (CL). Cytochrome c (cyt c) acts as a CL-specific peroxidase very early in apoptosis. At this stage, the hostile events are still secluded within the mitochondria and do not reach the cytosolic targets. CL oxidation process is required for the release of pro-apoptotic factors into the cytosol. Manipulation of cyt c interactions with CL, inhibition of peroxidase activity, and prevention of CL peroxidation are prime targets for the discovery of anti-apoptotic drugs acting before the "point-of-no-return" in the fulfillment of the cell death program. Therefore, mitochondria-targeted disruptors and inhibitors of cyt c/CL peroxidase complexes and suppression of CL peroxidation represent new strategies in anti-apoptotic drug discovery. [Description provided by NIOSH]
• Subjects:
  Biochemistry Biological Products Immune System Neoplasms Occupational Health Safety
• Keywords:
  Author Keywords: Apoptosis Bacterial-cultures Biochemical-analysis Biological-agents Biological-effects Cancer Cardiolipin Cell-biology Cell-damage Cell-metabolism Cellular-reactions Cellular-uptake Cytochrome C Drug Delivery Immune-reaction Mitochondria-targeting

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• ISSN:
  1613-4125
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; OSHA Region 6 ; Pennsylvania ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  104-114
• Volume:
  53
• Issue:
  1
• NIOSHTIC Number:
  nn:20034991
• Citation:
  Mol Nutr Food Res 2009 Jan; 53(1):104-114
• Contact Point Address:
  Dr. Valerian E. Kagan, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 100 Technology Drive, Suite 350, Pittsburgh, PA 15219-3130
• Email:
  kagan@pitt.edu
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  Molecular Nutrition & Food Research
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f0833675aa372b59c24d5266ea4adeddb8544b551d67d5d90692edec398581ce05ec5ef1ef8fe60457bb0fc0849c88f4d45ae988bc3d7d74d69f0b13bd889e4e
• Download URL:
  https://stacks.cdc.gov/view/cdc/186997/cdc_186997_DS1.pdf
• File Type:
  [PDF - 3.24 MB ]