title: Mitochondrial networking protects beta-cells from nutrient-induced apoptosis.
abstract: OBJECTIVE
  Previous studies have reported that beta-cell mitochondria exist as discrete organelles that exhibit heterogeneous bioenergetic capacity. To date, networking activity, and its role in mediating beta-cell mitochondrial morphology and function, remains unclear. In this article, we investigate beta-cell mitochondrial fusion and fission in detail and report alterations in response to various combinations of nutrients.
  
  
  METHODS
  Using matrix-targeted photoactivatable green fluorescent protein, mitochondria were tagged and tracked in beta-cells within intact islets, as isolated cells and as cell lines, revealing frequent fusion and fission events. Manipulations of key mitochondrial dynamics proteins OPA1, DRP1, and Fis1 were tested for their role in beta-cell mitochondrial morphology. The combined effects of free fatty acid and glucose on beta-cell survival, function, and mitochondrial morphology were explored with relation to alterations in fusion and fission capacity.
  
  
  RESULTS
  beta-Cell mitochondria are constantly involved in fusion and fission activity that underlies the overall morphology of the organelle. We find that networking activity among mitochondria is capable of distributing a localized green fluorescent protein signal throughout an isolated beta-cell, a beta-cell within an islet, and an INS1 cell. Under noxious conditions, we find that beta-cell mitochondria become fragmented and lose their ability to undergo fusion. Interestingly, manipulations that shift the dynamic balance to favor fusion are able to prevent mitochondrial fragmentation, maintain mitochondrial dynamics, and prevent apoptosis.
  
  
  CONCLUSIONS
  These data suggest that alterations in mitochondrial fusion and fission play a critical role in nutrient-induced beta-cell apoptosis and may be involved in the pathophysiology of type 2 diabetes.
authors: Department of Molecular Medicine, Obesity Research Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors: Anthony J A
authors: AJ
authors: Molina
authors: Jakob D
authors: JD
authors: Wikstrom
authors: Linsey
authors: L
authors: Stiles
authors: Guy
authors: G
authors: Las
authors: Hibo
authors: H
authors: Mohamed
authors: Alvaro
authors: A
authors: Elorza
authors: Gil
authors: G
authors: Walzer
authors: Gilad
authors: G
authors: Twig
authors: Steve
authors: S
authors: Katz
authors: Barbara E
authors: BE
authors: Corkey
authors: Orian S
authors: OS
authors: Shirihai
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000235:genetics; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000502:physiology; D008561:Membrane Fusion / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000502:physiology
chemical_list: D049452:Green Fluorescent Proteins; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse