Impaired Bioenergetics in Clinical Medicine: A Target to Tackle

Abstract

Mitochondrial energy deficit is considered a key element of different clinical pathologies -from inherited disorders of energy metabolism to drug-induced mitochondrial toxicity, to cardiometabolic and neurodegenerative diseases. However, clinical manifestations of impaired bioenergetics are not easy to recognize, with patient-reported features usually include non-pathognomonic fatigue and weakness, or exercise intolerance, while specific lab tests are missing. Although it is not clear whether poor energetics is a primary deficit or a secondary consequence of specific disorders, improving mitochondrial viability remains a challenging task in both experimental and clinical medicine. In this review, biochemical and clinical evidence of energy deficits were reviewed, along with possible therapeutic options to tackle energy failure and restore bioenergetics.

Untargeted LC/MS-Based Metabolic Phenotyping of Hypopituitarism in Young Males

“…Mitochondrion is a key organelle in cellular bioenergetics. Mitochondrial dysfunction can not only rooted form inherited disorders, but also secondary MD-related diseases (e.g., type 2 diabetes, obesity and neurodegenerative diseases) ( Ostojic, 2017 ). As growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) has function on mitochondrial biogenesis, respiration and ATP production, oxidative stress, senescence, and apoptosis ( Poudel et al, 2020 ).…”

Using the NIH symptom science model to understand fatigue and mitochondrial bioenergetics

“…Mitochondria are the powerhouse of cells and play a key role in maintaining cellular functions and survival by producing ATP. Dysfunction in mitochondria can cause impaired mitochondrial bioenergetics that may be due to: (1) an inadequate number of mitochondria; (2) an inability to produce the needed substrates to mitochondria; and/or (3) a problem within the mitochondrial electron transport chain and ATP machinery [12].…”

“…The ATP molecule produced within the mitochondria serves as the primary source for cellular energy. Production of ATP is required for the preservation of normal cellular function [12], and higher quantities of mitochondria can be found in cardiac muscle, brain cells, and skeletal muscles that require more ATP to function [46]. The majority of ATP is produced in the mitochondria by a process called cellular respiration (Figure 2).…”

“…The ability to generate energy in the mitochondria is related to the production and utilization of the molecule called ATP. ATP is produced within the mitochondria during oxidative phosphorylation [12]. In the mitochondria the metabolism of sugars are completed and approximately 30 molecules of ATP are produced for each molecule of glucose oxidized.…”

N-Acetylaspartate-to-creatine ratio in twelve brain locations among healthy men and women with different levels of education

“…The human brain is a high energy-consuming organ, and delicate homeostasis of brain bioenergetics appears to be affected by many intrinsic and extrinsic factors. Impaired brain bioenergetics is often associated with aging, neurodegenerative diseases, neoplasms or inherited disorders [1], with concentrations of different energy-related brain metabolites routinely used as indicators of brain functionality. N-acetylaspartate-to-creatine ratio (NAA/Cr) has proved to be a relevant marker to evaluate brain-specific bioenergetics in the setting of impaired energy metabolism and neuronal injury of various genesis [2].…”