Growth factor erv1-like modulates Drp1 to preserve mitochondrial dynamics and function in mouse embryonic stem cells.
The relationship of mitochondrial dynamics and function to pluripotency are rather poorly understood aspects of stem cell biology. Here we show that growth factor erv1-like (Gfer) is involved in preserving mouse embryonic stem cell (ESC) mitochondrial morphology and function. Knockdown (KD) of Gfer in ESCs leads to decreased pluripotency marker expression, embryoid body (EB) formation, cell survival, and loss of mitochondrial function. Mitochondria in Gfer-KD ESCs undergo excessive fragmentation and mitophagy, whereas those in ESCs overexpressing Gfer appear elongated. Levels of the mitochondrial fission GTPase dynamin-related protein 1 (Drp1) are highly elevated in Gfer-KD ESCs and decreased in Gfer-overexpressing cells. Treatment with a specific inhibitor of Drp1 rescues mitochondrial function and apoptosis, whereas expression of Drp1-dominant negative resulted in the restoration of pluripotency marker expression in Gfer-KD ESCs. Altogether, our data reveal a novel prosurvival role for Gfer in maintaining mitochondrial fission-fusion dynamics in pluripotent ESCs.
Todd
Lance R
LR
James Graham Brown Cancer Center, University of Louisville, Owensboro, KY 42303, USA.
Damin
Matthew N
MN
Gomathinayagam
Rohini
R
Horn
Sarah R
SR
Means
Anthony R
AR
Sankar
Uma
U
D000818:Animals; D002460:Cell Line; D003579:Cytochrome Reductases / Q000378:metabolism*; D034281:Dynamins; D053595:Embryonic Stem Cells / Q000166:cytology*; D020558:GTP Phosphohydrolases / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics / Q000502:physiology*
D008869:Microtubule-Associated Proteins; D003579:Cytochrome Reductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C551231:GFER protein, mouse; D020558:GTP Phosphohydrolases; C486391:Dnm1l protein, mouse; D034281:Dynamins