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Charles Darwin's Mitochondrial Disorder: Possible Neuroendocrine Involvement.

ABSTRACT: Charles Darwin, the famous naturalist, suffered relapsing, debilitating illness for most of his adult life with a plethora of symptoms. The diagnosis favoured here for this illness is that of an adult-onset mitochondrial disorder due to a maternally inherited, pathological mitochondrial DNA mutation clinically manifesting as MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome. This diagnosis accounts for Darwin's primary symptoms; in addition, it accounts for the various unusual illnesses that afflicted his siblings and maternal (Wedgwood) ancestors. Symptoms of Darwin's illness may be related to dysfunction of cells with high energy requirements; this includes cells constituting the cardiac conduction system, cerebral endothelial cells, neurons, neuroepithelial cells of the vestibular apparatus, and, as proposed here, central and peripheral neuroendocrine cells. Although Darwin's episodes of sudden facial flushing, his nocturnal panic attacks, and his severe gastrointestinal symptoms are not readily explained, these symptoms may relate to neuroendocrine dysfunction, either an uncontrolled release of stimulatory hormone or impaired inhibitory control. It is also conceivable that the autonomic system had been involved. A study of Darwin's illness may benefit those who suffer from similar symptoms today.

SUBMITTER: Hayman J

PROVIDER: S-EPMC8710138 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMitochondrial dysfunctions play a pivotal role in cerebral ischemia-reperfusion (I/R) injury. Although mitochondrial transplantation has been recently explored for the treatment of cerebral I/R injury, the underlying mechanisms and fate of transplanted mitochondria are still poorly understood.MethodsMitochondrial morphology and function were assessed by fluorescent staining, electron microscopy, JC-1, PCR, mitochondrial stress testing, and metabolomics. Therapeutic effects of mitochondria were evaluated by cell viability, reactive oxygen species (ROS), and apoptosis levels in a cellular hypoxia-reoxygenation model. Rat middle cerebral artery occlusion model was applied to assess the mitochondrial therapy in vivo. Transcriptomics was performed to explore the underlying mechanisms. Mitochondrial fate tracking was implemented by a variety of fluorescent labeling methods.ResultsNeuro-2a (N2a) cell-derived mitochondria had higher mitochondrial membrane potential, more active oxidative respiration capacity, and less mitochondrial DNA copy number. Exogenous mitochondrial transplantation increased cellular viability in an oxygen-dependent manner, decreased ROS and apoptosis levels, improved neurobehavioral deficits, and reduced infarct size. Transcriptomic data showed that the differential gene enrichment pathways are associated with metabolism, especially lipid metabolism. Mitochondrial tracking indicated specific parts of the exogenous mitochondria fused with the mitochondria of the host cell, and others were incorporated into lysosomes. This process occurred at the beginning of internalization and its efficiency is related to intercellular connection.ConclusionsMitochondrial transplantation may attenuate cerebral I/R injury. The mechanism may be related to mitochondrial component separation, altering cellular metabolism, reducing ROS, and apoptosis in an oxygen-dependent manner. The way of isolated mitochondrial transfer into the cell may be related to intercellular connection.

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Charles Darwin's Mitochondrial Disorder: Possible Neuroendocrine Involvement.

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