Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells

Details

• Personal Author:
  Amoscato AA ; Bahar I ; Balasubramanian K ; Baty C ; Bayir H ; Borisenko G ; Cheikhi A ; Chu CT ; Dagda RK ; Gusdon AM ; Huang Z ; Ji J ; Jiang JF ; Kagan VE ; Kapralov AA ; Klein-Seetharaman J ; Mohammadyani D ; Qiang-Wang KZ ; Shrivastava IH ; Steer EK ; Tyurin VA ; Tyurina YY ; Wang R ; Watkins S ; Yanamala N ; Zhu J
• Description:
  Recognition of injured mitochondria for degradation by macroautophagy is essential for cellular health, but the mechanisms remain poorly understood. Cardiolipin is an inner mitochondrial membrane phospholipid. We found that rotenone, staurosporine, 6-hydroxydopamine and other pro-mitophagy stimuli caused externalization of cardiolipin to the mitochondrial surface in primary cortical neurons and SH-SY5Y cells. RNAi knockdown of cardiolipin synthase or of phospholipid scramblase-3, which transports cardiolipin to the outer mitochondrial membrane, decreased the delivery of mitochondria to autophagosomes. Furthermore, we found that the autophagy protein microtubule-associated-protein-1 light chain 3 (LC3), which mediates both autophagosome formation and cargo recognition, contains cardiolipin-binding sites important for the engulfment of mitochondria by the autophagic system. Mutation of LC3 residues predicted as cardiolipin-interaction sites by computational modelling inhibited its participation in mitophagy. These data indicate that redistribution of cardiolipin serves as an 'eat-me' signal for the elimination of damaged mitochondria from neuronal cells. [Description provided by NIOSH]
• Subjects:
  Biomechanical Phenomena Occupational Health Safety
• Keywords:
  Biological-effects Biological-function Biomechanics Cell-biology Cell-function Cellular-function Proteins
• ISSN:
  1465-7392
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Nevada ; OSHA Region 3 ; OSHA Region 9 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  15
• Issue:
  10
• NIOSHTIC Number:
  nn:20043371
• Citation:
  Nat Cell Biol 2013 Oct; 15(10):1197-1205
• Contact Point Address:
  Charleen T. Chu, Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213
• Email:
  ctc4@pitt.edu
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Nature Cell Biology
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4c79c008bb982c2f38552eab845f2573637915476835e8855f36c1e9c0a5f24c7a74e762cea7bd04819040c5e57e358d4f2fcb6966fbc78e28cba5a40480cdbf
• Download URL:
  https://stacks.cdc.gov/view/cdc/195288/cdc_195288_DS1.pdf
• File Type:
  [PDF - 6.74 MB ]