TY - JOUR
T1 - SUMOylation of mitofusins
T2 - A potential mechanism for perinuclear mitochondrial congression in cells treated with mitochondrial stressors
AU - Kim, Catherine
AU - Juncker, Meredith
AU - Reed, Ryan
AU - Haas, Arthur
AU - Guidry, Jessie
AU - Matunis, Michael
AU - Yang, Wei Chih
AU - Schwartzenburg, Joshua
AU - Desai, Shyamal
N1 - Funding Information:
These studies were supported by NIH/NINDS R21NS060960 grant to SD. We thank Dr. David Chan (Division of Biology and the Howard Hughes Medical Institute, California Institute of Technology, USA) for providing reagents, his valuable suggestions and advice throughout this project. We also thank Dr. Edward Wojcik (Department of Biochemistry and Molecular Biology, LSU-School of Medicine, New Orleans, USA) for his expertise, assistance, and providing reagents to CK for microscopy studies.
Funding Information:
These studies were supported by NIH / NINDS R21NS060960 grant to SD. We thank Dr. David Chan (Division of Biology and the Howard Hughes Medical Institute, California Institute of Technology, USA) for providing reagents, his valuable suggestions and advice throughout this project. We also thank Dr. Edward Wojcik (Department of Biochemistry and Molecular Biology, LSU-School of Medicine, New Orleans, USA) for his expertise, assistance, and providing reagents to CK for microscopy studies.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - 26S proteasome
KW - Autophagy
KW - Mitochondria
KW - Mitofusin
KW - Mitophagy
KW - Small ubiquitin modifier (SUMO)
KW - Ubiquitin
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U2 - 10.1016/j.bbadis.2021.166104
DO - 10.1016/j.bbadis.2021.166104
M3 - Article
C2 - 33617988
AN - SCOPUS:85102053096
SN - 0925-4439
VL - 1867
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 6
M1 - 166104
ER -