Dysregulated mitochondrial and chloroplast bioenergetics from a translational medical perspective (Review)

Abstract

Mitochondria and chloroplasts represent endosymbiotic models of complex organelle development, driven by intense evolutionary pressure to provide exponentially enhanced ATP-dependent energy production functionally linked to cellular respiration and photosynthesis. Within the realm of translational medicine, it has become compellingly evident that mitochondrial dysfunction, resulting in compromised cellular bioenergetics, represents a key causative factor in the etiology and persistence of major diseases afflicting human populations. As a pathophysiological consequence of enhanced oxygen utilization that is functionally uncoupled from the oxidative phosphorylation of ADP, significant levels of reactive oxygen species (ROS) may be generated within mitochondria and chloroplasts, which may effectively compromise cellular energy production following prolonged stress/inflammatory conditions. Empirically determined homologies in biochemical pathways, and their respective encoding gene sequences between chloroplasts and mitochondria, suggest common origins via entrapped primordial bacterial ancestors. From evolutionary and developmental perspectives, the elucidation of multiple biochemical and molecular relationships responsible for errorless bioenergetics within mitochondrial and plastid complexes will most certainly enhance the depth of translational approaches to ameliorate or even prevent the destructive effects of multiple disease states. The selective choice of discussion points contained within the present review is designed to provide theoretical bases and translational insights into the pathophysiology of human diseases from a perspective of dysregulated mitochondrial bioenergetics with special reference to chloroplast biology.

Microbiota and Neurological Disorders: A Gut Feeling

“… 61 There is supporting evidence to suggest that our microbiome plays a fundamental role in this relationship. 14 , 62 , 63 Numerous studies 64 , 65 show microbe-generated metabolites are intertwined with host cell biochemistry and physiology, and SCFA-mediated cell signaling is a key pathway that gut microbes use to communicate with the host. 9 , 44 , 66–68 Acetate, propionate (propionic acid is also commonly referred to as PPA), butyrate, and pentanoate, having respectively, 2, 3, 4, and 5 carbon atoms are SCFAs ( Table 1 ), largely produced by microbial fermentation of complex polysaccharides (starches and fibers) in the colon (longer chain aliphatic acids with 6 to 12 carbons are considered to be medium-chain fatty acids [MCFAs]).…”

Augmentation of Whole-Body Metabolic Status by Mind-Body Training: Synchronous Integration of Tissue- and Organ-Specific Mitochondrial Function

“…As a key biochemical corollary, potential health benefits of behaviorally-mediated enhancements of coordinated respiratory rhythms and pulmonary gas exchange are critically linked to homeostatic maintenance of state-dependent changes in tissue oxygenation and regulated mitochondrial respiration. Accordingly, we have elaborated and extend a proposed mechanism of action linking mind-body training exercises to enhanced metabolic advantage and cellular ATP production that is critically linked to synchronized mitochondrial function involving physiological activation of O 2 -dependent recycling of nitric oxide (NO) and inorganic nitrite by intra-mitochondrial nitrite reductases [29–32] (Figure 2). Interestingly, a prior clinical study has drawn a potentially important association of RR training with a reduction in volumetric O 2 consumption linked to enhanced concentrations of exhaled NO [4,33].…”

Alkaloids, Nitric Oxide, and Nitrite Reductases: Evolutionary Coupling as Key Regulators of Cellular Bioenergetics with Special Relevance to the Human Microbiome

“…These prior observations relating to mitochondrial opiate receptors were functionally confirmed by a recent publication from our laboratory demonstrating morphine/μ3 opiate receptor mediated NO release from isolated human mitochondria [ 65 ]. As discussed in depth above, we propose the regulatory effects of “morphinergic” coupling to cNOS activation on mitochondrial function and cellular bioenergetics are synergistically amplified by coordinate activation of cellular and mitochondrial nitrite reductases [ 27 , 28 , 35 , 66 ].…”