Diet, Muscle Protein Synthesis and Autophagy Relationships in Cancer. An Attempt to Understand Where Are We Going, and Why

Protein-based structures are indispensable to maintain life,
so identification and removal of worn out structures achieved
through proteostasis, the sum of micro and macro-autophagy
(autophagy) plus ubiquitin-proteasome system, must balance
renewal by new synthesis. Many of the elements controlling
dynamically equilibria between protein synthesis and protein
degradation have been identified and modalities of activation
actively studied, still we are quite far from mastering how this
balance is ruled. Failure to maintain a positive balance
between protein synthesis and protein degradation would
result in sarcopenia, defined as the loss of skeletal muscle
mass and function, a major clinical problem frequently
accompanying chronic illnesses, but peculiarly spotted in
cancer and in elderly patients. Also, how cancer is fed, and
how nutrition in cancer patients may affect evolution and
therapy effectiveness is another field of opinions and
uncertainty. On the other hand, exercise and nutrition tailored
to provide adequate amounts of amino acids are widely
considered a necessary strategy for prevention and treatment
of protein synthetic deficits in muscles. This paper will
synthetically review how different nutritional strategies and
energy production may interconnect efficiently synthesis and
scavenging of aged and overused protein molecules by
autophagy. Finally, since energy availability rules life and
death of cells and organisms, an hypothesis predicting how
energy may control the ratios among protein synthesis and
autophagy is proposed: in normal conditions, protein syntheses
have a key role in autophagy activation by consuming large
amounts of energy when forming peptidic bonds, that is
adenosine tri-phosphate (ATP) is consumed to monophospahate (AMP), thus decreasing ATP to AMP ratios.
Conversely, both protein syntheses and autophagy may be
scarcely activated when low availability of ATP would result
also in lowest concentrations of AMP. In this peculiar setting,
reduced rates of both protein syntheses and autophagy would
be observed, resulting in worsening of protein balance and
functions.