Growth factor erv1-like modulates Drp1 to preserve mitochondrial dynamics and function in mouse embryonic stem cells.
Journal Article (Journal Article)
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.
Full Text
- Published version (via Digital Object Identifier)
- Pubmed Central version
- Open Access Copy from Duke
- Link to Item
Duke Authors
Cited Authors
- Todd, LR; Damin, MN; Gomathinayagam, R; Horn, SR; Means, AR; Sankar, U
Published Date
- April 1, 2010
Published In
Volume / Issue
- 21 / 7
Start / End Page
- 1225 - 1236
PubMed ID
- 20147447
Pubmed Central ID
- PMC2847526
Electronic International Standard Serial Number (EISSN)
- 1939-4586
Digital Object Identifier (DOI)
- 10.1091/mbc.e09-11-0937
Language
- eng
Conference Location
- United States