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George B. Stefano, Joshua Samuel, Richard M. Kream
(Department of Research, MitoGenetics Research Institute, Farmingdale, NY, USA)
Med Sci Monit 2017; 23:101-106
Clinical usage of several classes of antibiotics is associated with moderate to severe side effects due to the promotion of mitochondrial dysfunction. We contend that this may be due to perturbation of unique evolutionary relationships that link selective biochemical and molecular aspects of mitochondrial biology to conserved enzymatic processes derived from bacterial progenitors. Operationally, stereo-selective conformational matching between mitochondrial respiratory complexes, cytosolic and nuclear signaling complexes appears to support the conservation of a critically important set of chemical messengers required for existential regulation of homeostatic cellular processes. Accordingly, perturbation of normative mitochondrial function by select classes of antibiotics is certainly reflective of the high degree of evolutionary pressure designed to maintain ongoing bidirectional signaling processes between cellular compartments. These issues are of critical importance in evaluating potentially severe side effects of antibiotics on complex behavioral functions mediated by CNS neuronal groups. The CNS is extremely dependent on delivery of molecular oxygen for maintaining a required level of metabolic activity, as reflected by the high concentration of neuronal mitochondria. Thus, it is not surprising to find several distinct behavioral abnormalities conforming to established psychiatric criteria that are associated with antibiotic usage in humans. The manifestation of acute and/or chronic psychiatric conditions following antibiotic usage may provide unique insights into key etiological factors of major psychiatric syndromes that involve rundown of cellular bioenergetics via mitochondrial dysfunction. Thus, a potential window of opportunity exists for development of novel therapeutic agents targeting diminished mitochondrial function as a factor in severe behavioral disorders.