Tuesday, 19 August 2014

Deletion of the Mitochondrial Chaperone TRAP-1 Uncovers Global Reprogramming of Metabolic Networks.

Deletion of the Mitochondrial Chaperone TRAP-1 Uncovers Global Reprogramming of Metabolic Networks.

Chaperones are protein complexes which are used in the transport & folding of other cellular proteins. The authors found that deletion of the mitochondrial chaperone TRAP-1 led to a viable mouse model with reduced signs of ageing and age-associated pathologies such as obesity, dysplasia and tumour formation.

On a cellular level, TRAP-1 knockout reduced mitochondrial respiration, possibly by affecting complex II formation, leading to an upregulation in glyolytic activity. Somewhat paradoxically, the oxidative phosphorylation transcriptome was significantly upregulated, with a larger increase in complexes III and IV transcripts. Hsp90 (a similar chaperone) was upregulated and transported to the mitochondria in what may be a compensatory response.

Cell cultures showed reduced proliferation consistent with cell-cycle arrest, and showed a small but significant increase in ROS production.

The authors suggest that TRAP-1 knockout impairs successful folding of the SDHB subunit of complex II, which is partially rescued by dramatically upregulating all elements of oxidative phosphorylation and partially compensated for by reduced glycolysis.

It is unclear whether the cell's ability to generate energy from its mitochondria is impaired, or if the cell simply has to create more oxphos complexes to do so, however a small increase in ROS is observed, which may have a protective effect via mitohormesis and thus play a role in protecting the mice from age-associated pathologies.

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