SUMOylation of mitofusins: A potential mechanism for perinuclear mitochondrial congression in cells treated with mitochondrial stressors

Catherine Kim, Meredith Juncker, Ryan Reed, Arthur Haas, Jessie Guidry, Michael Matunis, Wei Chih Yang, Joshua Schwartzenburg, Shyamal Desai

Research output: Contribution to journalArticlepeer-review

Abstract

Depolarized/damaged mitochondria aggregate at the perinuclear region prior to mitophagy in cells treated with mitochondrial stressors. However, the cellular mechanism(s) by which damaged mitochondria are transported and remain aggregated at the perinuclear region is unknown. Here, we demonstrate that mitofusins (Mfn1/2) are post-translationally modified by SUMO2 (Small Ubiquitin-related Modifier 2) in Human embryonic kidney 293 (Hek293) cells treated with protonophore CCCP and proteasome inhibitor MG132, both known mitochondrial stressors. SUMOylation of Mfn1/2 is not for their proteasomal degradation but facilitate mitochondrial congression at the perinuclear region in CCCP- and MG132-treated cells. Additionally, congressed mitochondria (mito-aggresomes) colocalize with LC3, ubiquitin, and SUMO2 in CCCP-treated cells. Knowing that SUMO functions as a “molecular glue” to facilitate protein-protein interactions, we propose that SUMOylation of Mfn1/2 may congress, glues, and confines damaged mitochondria to the perinuclear region thereby, protectively quarantining them from the heathy mitochondrial network until their removal via mitophagy in cells.

Original languageEnglish (US)
Article number166104
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1867
Issue number6
DOIs
StatePublished - Jun 1 2021

Keywords

  • 26S proteasome
  • Autophagy
  • Mitochondria
  • Mitofusin
  • Mitophagy
  • Small ubiquitin modifier (SUMO)
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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