Pyruvate dehydrogenase complex and nicotinamide nucleotide transhydrogenase constitute an energy-consuming redox circuit.
Biochem J
; 467(2): 271-80, 2015 Apr 15.
Article
in En
| MEDLINE
| ID: mdl-25643703
ABSTRACT
Cellular proteins rely on reversible redox reactions to establish and maintain biological structure and function. How redox catabolic (NAD+/NADH) and anabolic (NADP+/NADPH) processes integrate during metabolism to maintain cellular redox homoeostasis, however, is unknown. The present work identifies a continuously cycling mitochondrial membrane potential (ΔΨm)-dependent redox circuit between the pyruvate dehydrogenase complex (PDHC) and nicotinamide nucleotide transhydrogenase (NNT). PDHC is shown to produce H2O2 in relation to reducing pressure within the complex. The H2O2 produced, however, is effectively masked by a continuously cycling redox circuit that links, via glutathione/thioredoxin, to NNT, which catalyses the regeneration of NADPH from NADH at the expense of ΔΨm. The net effect is an automatic fine-tuning of NNT-mediated energy expenditure to metabolic balance at the level of PDHC. In mitochondria, genetic or pharmacological disruptions in the PDHC-NNT redox circuit negate counterbalance changes in energy expenditure. At the whole animal level, mice lacking functional NNT (C57BL/6J) are characterized by lower energy-expenditure rates, consistent with their well-known susceptibility to diet-induced obesity. These findings suggest the integration of redox sensing of metabolic balance with compensatory changes in energy expenditure provides a potential mechanism by which cellular redox homoeostasis is maintained and body weight is defended during periods of positive and negative energy balance.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyruvate Dehydrogenase Complex
/
Membrane Potential, Mitochondrial
/
NADP Transhydrogenase, AB-Specific
/
Hydrogen Peroxide
/
Mitochondria, Muscle
/
NADP
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biochem J
Year:
2015
Document type:
Article
Affiliation country:
United States