Merck
  • Home
  • Search Results
  • Manganese superoxide dismutase deficiency triggers mitochondrial uncoupling and the Warburg effect.

Manganese superoxide dismutase deficiency triggers mitochondrial uncoupling and the Warburg effect.

Oncogene (2014-11-05)
Y Xu, S Miriyala, F Fang, V Bakthavatchalu, T Noel, D M Schell, C Wang, W H St Clair, D K St Clair
ABSTRACT

Manganese superoxide dismutase (MnSOD) is a mitochondrially localized primary antioxidant enzyme, known to be essential for the survival of aerobic life and to have important roles in tumorigenesis. Here, we show that MnSOD deficiency in skin tissues of MnSOD-heterozygous knockout (Sod2(+/-)) mice leads to increased expresson of uncoupling proteins (UCPs). When MnSOD is deficient, superoxide radical and its resulting reactive oxygen species (ROS) activate ligand binding to peroxisome proliferator-activated receptor alpha (PPARα), suggesting that the activation of PPARα signaling is a major mechanism underlying MnSOD-dependent UCPs expression that consequently triggers the PI3K/Akt/mTOR pathway, leading to increased aerobic glycolysis. Knockdown of UCPs and mTOR suppresses lactate production and increases ATP levels, suggesting that UCPs contribute to increased glycolysis. These results highlight the existence of a free radical-mediated mechanism that activates mitochondria uncoupling to reduce ROS production, which precedes the glycolytic adaptation described as the Warburg Effect.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Rapamycin, Ready Made Solution, 2.5 mg/mL in DMSO (2.74 mM), from Streptomyces hygroscopicus
Sigma-Aldrich
Dihydroethidium, ≥95%
Sigma-Aldrich
Dihydroethidium, BioReagent, suitable for fluorescence, ≥95% (HPCE)
Sigma-Aldrich
2-Chloro-5-nitrobenzanilide, 97%
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Sod2
Sigma-Aldrich
2-Chlorophenol, ≥99%
Sigma-Aldrich
2-Chlorophenol, 98%
Sigma-Aldrich
GW9662, >98% (HPLC)
Sigma-Aldrich
MISSION® esiRNA, targeting human SOD2