Life Cycle of an Energy Producing Protein

ATP synthase is a most amazing molecular machine found in mitochondria that produces ATP, the cell’s most important energy carrier, its main component rotates at 300 cycles per second driven by a cascade of 1,000 hydrogen ions to produce a hundred ATP molecules a second.

I want to use the life cycle of this molecular machine, which makes life as we know possible, to illustrate the importance of obligatory recycling of living material and the influence of lifestyle decisions on those processes.  ATP synthase has a half life of around 40 hours, therefore no ATP synthase exist in your body for longer than 5 days. This means that every living cell has to dismantle and rebuild all of its ATP synthase within 5 days and in order to maintain a stable energy supply without excessive accumulation of waste material, the production of new ATP synthase must be matched with the recycling of old:  this is a hugely expensive undertaking in terms of energy and resources for the organism and clearly must be necessary for survival.  The reason for such a high turnover of all proteins in the body is that they become damaged and dysfunctional quite rapidly. Specific identification and removal of dysfunctional proteins is complex and highly regulated, carried out in proteosomes and a process called autophagy. Deficiencies in autophagy are thought to be responsible for many degenerative conditions such as dementia, Parkinson’s, and aging in general.  A lethal childhood condition Batten Disease, is caused by inadequate dismantling and therefore intracellular build up of dysfunctional ATP synthase proteins.

So how do lifestyle decisions affect protein synthesis and autophagy? Diet and Exercise!

Nutritional factors have a major controlling influence on autophagy; high levels of amino acids and glucose suppress autophagy and fasting particularly starvation powerfully activates it. The main pathway to suppress autophagy is through a master-controller (mTOR) that is controlled amongst other factors by insulin and glucagon, note that these hormones are regulated primarily by blood glucose levels and to a lesser degree amino-acids.  Simply put glucose and amino-acids suppress autophagy while low levels of both enhance it.  Many of the health benefits of calorie restriction are though to be due to activation of autophagy.  However enhancement of autophagy may also be achieved by  specific avoidance of raised glucose and excessive protein intake without the difficulties associated with generalized calorie restriction.

On the synthesis side diet; acting through insulin and glucagon, as well as exercise and other environmental circumstances have a controlling influence on  muscle and mitochondrial biosynthesis acting through the master-controller transcription factor (PGC1alpha), as seen in the figure below from this linked reference.

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