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Formation of elongated giant mitochondria in DFO-induced cellular senescence: involvement of enhanced fusion process through modulation of Fis1.

Authors
Yoon, YS; Yoon, DS; Lim, IK; Yoon, SH; Chung, HY; Rojo, M; Malka, F; Jou, MJ; Martinou, JC; Yoon, G
Citation
Journal of cellular physiology, 209(2):468-480, 2006
Journal Title
Journal of cellular physiology
ISSN
0021-95411097-4652
Abstract
Enlarged or giant mitochondria have often been documented in aged tissues although their role and underlying mechanism remain unclear. We report here how highly elongated giant mitochondria are formed in and related to the senescent arrest. The mitochondrial morphology was progressively changed to a highly elongated form during deferoxamine (DFO)-induced senescent arrest of Chang cells, accompanied by increase of intracellular ROS level and decrease of mtDNA content. Interestingly, under exposure to subcytotoxic doses of H2O2 (200 microM), about 65% of Chang cells harbored elongated mitochondria with senescent phenotypes whereas ethidium bromide (EtBr) (50 ng/ml) only reformed the cristae structure. Elongated giant mitochondria were also observed in TGF beta1- or H2O2-induced senescent Mv1Lu cells and in old human diploid fibroblasts (HDFs). In all senescent progresses employed in this study Fis1 protein, a mitochondrial fission modulator, was commonly downexpressed. Overexpression of YFP-Fis1 reversed both mitochondrial elongation and appearance of senescent phenotypes induced by DFO, implying its critical involvement in the arrest. Finally, we found that direct induction of mitochondrial elongation by blocking mitochondrial fission process with Fis1-DeltaTM or Drp1-K38A was sufficient to develop senescent phenotypes with increased ROS production. These data suggest that mitochondrial elongation may play an important role as a mediator in stress-induced premature senescence.
MeSH terms
AnimalsCell Aging/drug effects*Cells, CulturedChildDNA, Mitochondrial/metabolismDeferoxamine/pharmacology*Ethidium/metabolismFibroblasts/cytologyFibroblasts/drug effectsGene Expression/drug effectsHumansHydrogen Peroxide/pharmacologyIron Chelating Agents/pharmacologyMaleMembrane Fusion/drug effects*Membrane ProteinsMitochondria/metabolism*Mitochondria/pathology*Mitochondria/ultrastructureMitochondrial Membranes/drug effectsMitochondrial Proteins/metabolism*PhenotypeRecombinant Fusion Proteins/metabolismTransforming Growth Factor beta/pharmacologyTransforming Growth Factor beta1
DOI
10.1002/jcp.20753
PMID
16883569
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
AJOU Authors
임, 인경윤, 수한윤, 계순
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