Formation of elongated giant mitochondria in DFO-induced cellular senescence: Involvement of enhanced fusion process through modulation of Fis1
✍ Scribed by Young-Sil Yoon; Dong-Sun Yoon; In Kyoung Lim; Soo-Han Yoon; Hae-Young Chung; Manuel Rojo; Florence Malka; Mei-Jie Jou; Jean-Claude Martinou; Gyesoon Yoon
- Book ID
- 102882573
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 818 KB
- Volume
- 209
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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 H~2~O~2~ (200 µM), 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 β1‐ or H~2~O~2~‐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‐ΔTM 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. J. Cell. Physiol. 209: 468–480, 2006. © 2006 Wiley‐Liss, Inc.