Bioenergetics and translational metabolism: implications for genetics, physiology and precision medicine

Abstract

It is now becoming clear that human metabolism is extremely plastic and varies substantially between healthy individuals. Understanding the biochemistry that underlies this physiology will enable personalized clinical interventions related to metabolism. Mitochondrial quality control and the detailed mechanisms of mitochondrial energy generation are central to understanding susceptibility to pathologies associated with aging including cancer, cardiac and neurodegenerative diseases. A precision medicine approach is also needed to evaluate the impact of exercise or caloric restriction on health. In this review, we discuss how technical advances in assessing mitochondrial genetics, cellular bioenergetics and metabolomics offer new insights into developing metabolism-based clinical tests and metabolotherapies. We discuss informatics approaches, which can define the bioenergetic-metabolite interactome and how this can help define healthy energetics. We propose that a personalized medicine approach that integrates metabolism and bioenergetics with physiologic parameters is central for understanding the pathophysiology of diseases with a metabolic etiology. New approaches that measure energetics and metabolomics from cells isolated from human blood or tissues can be of diagnostic and prognostic value to precision medicine. This is particularly significant with the development of new metabolotherapies, such as mitochondrial transplantation, which could help treat complex metabolic diseases.

Preference and detrimental effects of high fat, sugar, and salt diet in wild‐caught Drosophila simulans are reversed by flight exercise

“…A growing body of evidence suggests that the harmful effects of excessive caloric intake and associated health ailments can be mitigated or even reversed by physical exercise in mammals 38 . To determine whether the negative effects of WD can be prevented by exercise in the fruit fly model, 3 to 4‐day‐old adult male flies were randomly assigned to one of the following four groups: 1) control sedentary flies on CD; 2) sedentary flies on WD; 3) exercise flies on CD (CDE); 4) exercise flies on WD (WDE).…”

“…A growing body of evidence suggests that the harmful effects of excessive caloric intake and associated health ailments can be mitigated or even reversed by physical exercise in mammals (38).…”

Quantitative and Molecular Similarity Analyses of the Metabolites of Cold- and Hot-Natured Chinese Herbs

“…While discussing the effects of chemical compositions on the cold/hot natures of Chinese herbs, the theory of generalized oxidation and reduction was hypothesized to be associated with these kinds of thermal properties [ 31 ]. In general, metabolism of the human body can be broadly categorized into catabolism and anabolism [ 32 ]. In sharp contrast, cold-natured herbs consist of more amino acid compounds, which are the basic building blocks for the anabolic processes of cellular growth or function ( Figure 3 ).…”

A precision medicine approach to defining the impact of doxorubicin on the bioenergetic-metabolite interactome in human platelets

“…Taken together, these data builds upon the concept of how the metabolome in the platelets is integrated with bioenergetics and how platelets are viable as metabolic sensors in the context of environmental exposure and determination of severity of the toxic response among individuals. This study also has significant implications for precision medicine, in particular related to pathological conditions such as cancer and the utility of integrated approaches as exemplified by the bioenergetic-metabolite interactome [79].…”