Mitochondrial inherited genetic disorders are caused by mutations in nuclear genes or mitochondrial DNA encoding mitochondrial proteins. These mutations result in serious mitochondrial dysfunction that simultaneously compromises cell physiology in all tissues at various levels leading to multiorgan metabolic failures. These failures manifest clinically with devastating cardiomyopathy, hepatomegaly, hypoketotic hypoglycemia, rhabdomyolysis, myoglobinuria, brain injury, compromised hematopoietic tissue function, and many more. While primary defects occur or affect specific mitochondrial metabolic pathways, secondary mitochondrial diseases result from the toxic influences of endogenous metabolites to the mitochondria and/or cell physiology in general. The disturbances of the intricate balance of essential intermediates causing the dysfunction in multifunctional mitochondrial pathways are wide ranging and remain to be elucidated to better understand the impact of unrecognized mitochondrial dysfunction in human health in general.
The goal of this Research Topic is to provide the most advanced knowledge in mitochondrial genetic diseases to elucidate the mechanisms underlying the pathophysiology involved in the symptoms caused by the primary and secondary deficiencies and toxicities, with emphasis on the role of mitochondrial function in disease phenotype. Bioenergetic failure and oxidative stress have been extensively debated in the last 20 years as relevant pathomechanisms in these disorders, but little is known about the role of defects in other mitochondrial processes, such as biogenesis, dynamics, mitophagy, and the communication with other organelles. Also lacking is assessment of the toxic effect of increased alternative intermediates on mitochondrial proteins and their function. Therefore, the goal of this Research Topic is to have a more comprehensive medium of communicating the latest advances in the understanding of how defects in mitochondrial processes may affect the onset, severity, and heterogeneity of symptoms observed in patients with mitochondrial disorders. In addition, the issue aims to attract publications on finding innovative potential therapies to correct for the biochemical defects with methods that target mitochondria for modulating processes controlled by this organelle but aberrant due to defects or finding therapies to neutralize the toxicity of specific alternative compounds.
Research Articles:
•Mitochondrial bioenergetics
•Mitochondrial biogenesis and regulation
•Mitochondrial control of quality – fusion, fission and mitophagy
•Communication with other organelles, e.g., endoplasmic reticulum, lysosomes, and peroxisomes
•Therapeutics
?Small molecules: e.g., chaperone therapy, transcription enhancers, detoxification molecules
?Gene therapy and RNA based therapy
?Nutritional based therapy
Review Articles:
•Mitochondrial bioenergetics, fatty acid oxidation defect, TCA cycle defects, ETC defects
•Mitochondrial biogenesis and regulation
•Genotype/phenotype of specific diseases
•Potential therapies
Topic Editor Al-Walid Mohsen holds a patent and has other patent applications pending review related to fatty acid oxidation defects in mitochondria. Topic Editor Grant Hatch holds a patent related to mitochondrial dysfunction causing neurodegeneration. All Topic Editors declare no further competing interests with regard to the Research Topic subject.
Mitochondrial inherited genetic disorders are caused by mutations in nuclear genes or mitochondrial DNA encoding mitochondrial proteins. These mutations result in serious mitochondrial dysfunction that simultaneously compromises cell physiology in all tissues at various levels leading to multiorgan metabolic failures. These failures manifest clinically with devastating cardiomyopathy, hepatomegaly, hypoketotic hypoglycemia, rhabdomyolysis, myoglobinuria, brain injury, compromised hematopoietic tissue function, and many more. While primary defects occur or affect specific mitochondrial metabolic pathways, secondary mitochondrial diseases result from the toxic influences of endogenous metabolites to the mitochondria and/or cell physiology in general. The disturbances of the intricate balance of essential intermediates causing the dysfunction in multifunctional mitochondrial pathways are wide ranging and remain to be elucidated to better understand the impact of unrecognized mitochondrial dysfunction in human health in general.
The goal of this Research Topic is to provide the most advanced knowledge in mitochondrial genetic diseases to elucidate the mechanisms underlying the pathophysiology involved in the symptoms caused by the primary and secondary deficiencies and toxicities, with emphasis on the role of mitochondrial function in disease phenotype. Bioenergetic failure and oxidative stress have been extensively debated in the last 20 years as relevant pathomechanisms in these disorders, but little is known about the role of defects in other mitochondrial processes, such as biogenesis, dynamics, mitophagy, and the communication with other organelles. Also lacking is assessment of the toxic effect of increased alternative intermediates on mitochondrial proteins and their function. Therefore, the goal of this Research Topic is to have a more comprehensive medium of communicating the latest advances in the understanding of how defects in mitochondrial processes may affect the onset, severity, and heterogeneity of symptoms observed in patients with mitochondrial disorders. In addition, the issue aims to attract publications on finding innovative potential therapies to correct for the biochemical defects with methods that target mitochondria for modulating processes controlled by this organelle but aberrant due to defects or finding therapies to neutralize the toxicity of specific alternative compounds.
Research Articles:
•Mitochondrial bioenergetics
•Mitochondrial biogenesis and regulation
•Mitochondrial control of quality – fusion, fission and mitophagy
•Communication with other organelles, e.g., endoplasmic reticulum, lysosomes, and peroxisomes
•Therapeutics
?Small molecules: e.g., chaperone therapy, transcription enhancers, detoxification molecules
?Gene therapy and RNA based therapy
?Nutritional based therapy
Review Articles:
•Mitochondrial bioenergetics, fatty acid oxidation defect, TCA cycle defects, ETC defects
•Mitochondrial biogenesis and regulation
•Genotype/phenotype of specific diseases
•Potential therapies
Topic Editor Al-Walid Mohsen holds a patent and has other patent applications pending review related to fatty acid oxidation defects in mitochondria. Topic Editor Grant Hatch holds a patent related to mitochondrial dysfunction causing neurodegeneration. All Topic Editors declare no further competing interests with regard to the Research Topic subject.
