Genetically encoded tool for manipulation of ΔΨm identifies the latter as the driver of integrative stress response induced by ATP Synthase dysfunction.
Mangyu ChoeDenis V TitovPublished in: bioRxiv : the preprint server for biology (2023)
Mitochondrial membrane potential (ΔΨm) is one of the key parameters controlling cellular bioenergetics. Investigation of the role of ΔΨm in live cells is complicated by a lack of tools for its direct manipulation without off-target effects. Here, we adopted the uncoupling protein UCP1 from brown adipocytes as a genetically encoded tool for direct manipulation of ΔΨm. We validated the ability of exogenously expressed UCP1 to induce uncoupled respiration and lower ΔΨm in mammalian cells. UCP1 expression lowered ΔΨm to the same extent as chemical uncouplers but did not inhibit cell proliferation, suggesting that it manipulates ΔΨm without the off-target effects of chemical uncouplers. Using UCP1, we revealed that elevated ΔΨm is the driver of the Integrated Stress Response induced by ATP synthase inhibition in mammalian cells.
Keyphrases
- cell proliferation
- oxidative stress
- induced apoptosis
- poor prognosis
- adipose tissue
- cell cycle arrest
- binding protein
- single cell
- genome wide
- cell cycle
- metabolic syndrome
- gene expression
- type diabetes
- amino acid
- human health
- nitric oxide
- cell death
- long non coding rna
- small molecule
- protein protein
- risk assessment
- insulin resistance
- skeletal muscle
- signaling pathway
- network analysis