Docosahexaenoic acid mediates peroxisomal elongation, a prerequisite for peroxisome division

Akinori Itoyama, Masanori Honsho, Yuichi Abe, Ann Moser, Yumi Yoshida, Yukio Fujiki

Research output: Contribution to journalArticle

Abstract

Peroxisome division is regulated by several factors, termed fission factors, as well as the conditions of the cellular environment. Over the past decade, the idea of metabolic control of peroxisomal morphogenesis has been postulated, but remains largely undefined to date. In the current study, docosahexaenoic acid (DHA, C22:6n-3) was identified as an inducer of peroxisome division. In fibroblasts isolated from patients that carry defects in peroxisomal fatty acid β-oxidation, peroxisomes are much less abundant than normal cells. Treatment of these patient fibroblasts with DHA induced the proliferation of peroxisomes to the level seen in normal fibroblasts. DHA-induced peroxisomal proliferation was abrogated by treatment with a small inhibitory RNA (siRNA) targeting dynamin-like protein 1 and with dynasore, an inhibitor of dynamin-like protein 1, which suggested that DHA stimulates peroxisome division. DHA augmented the hyperoligomerization of Pex11pβ and the formation of Pex11pβ-enriched regions on elongated peroxisomes. Time-lapse imaging analysis of peroxisomal morphogenesis revealed a sequence of steps involved in peroxisome division, including elongation in one direction followed by peroxisomal fission. DHA enhanced peroxisomal division in a microtubule-independent manner. These results suggest that DHA is a crucial signal for peroxisomal elongation, a prerequisite for subsequent fission and peroxisome division.

Original languageEnglish (US)
Pages (from-to)589-602
Number of pages14
JournalJournal of cell science
Volume125
Issue number3
DOIs
StatePublished - Feb 1 2012

Keywords

  • Division
  • Dynamin-like protein 1
  • Elongation
  • Fatty acid β-oxidation
  • Fis1
  • Fission
  • Peroxin pex11p
  • Peroxisome morphogenesis

ASJC Scopus subject areas

  • Cell Biology

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