Pathogenic mitochondrial dysfunction and metabolic abnormalities
Walter H Moos1, Douglas V Faller2, Ioannis P Glavas3
1Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
Abstract:
Herein we trace links between biochemical pathways, pathogenesis, and metabolic diseases to set the stage for new therapeutic advances. Cellular and acellular microorganisms including bacteria and viruses are primary pathogenic drivers that cause disease. Missing from this statement are subcellular compartments, importantly mitochondria, which can be pathogenic by themselves, also serving as key metabolic disease intermediaries. The breakdown of food molecules provides chemical energy to power cellular processes, with mitochondria as powerhouses and ATP as the principal energy carrying molecule. Most animal cell ATP is produced by mitochondrial synthase; its central role in metabolism has been known for >80 years. Metabolic disorders involving many organ systems are prevalent in all age groups. Progressive pathogenic mitochondrial dysfunction is a hallmark of genetic mitochondrial diseases, the most common phenotypic expression of inherited metabolic disorders. Confluent genetic, metabolic, and mitochondrial axes surface in diabetes, heart failure, neurodegenerative disease, and even in the ongoing coronavirus pandemic.
Insights
Mitochondria, crucial for energy production, are implicated in metabolic diseases and pathogenesis. Understanding their role is key to developing new therapies for conditions like diabetes and neurodegenerative disorders.
Area of Science:
- Biochemistry
- Pathogenesis
- Metabolic Diseases
Background:
- Microorganisms like bacteria and viruses are known pathogenic drivers.
- Subcellular compartments, particularly mitochondria, are often overlooked as pathogenic factors and metabolic disease intermediaries.
- Mitochondria are essential for cellular energy production (ATP) and their dysfunction is central to many genetic and metabolic disorders.
Purpose of the Study:
- To explore the links between biochemical pathways, pathogenesis, and metabolic diseases.
- To highlight the critical role of mitochondria in disease etiology and progression.
- To set the stage for novel therapeutic strategies targeting mitochondrial dysfunction.
Main Methods:
- Review and synthesis of existing literature on biochemical pathways.
- Analysis of the role of mitochondria in pathogenesis.
- Connecting mitochondrial function to metabolic disorders.
Main Results:
- Mitochondria are not only essential for energy metabolism but can also be pathogenic independently.
- Mitochondrial dysfunction is a hallmark of genetic mitochondrial diseases and a common factor in broader metabolic disorders.
- Interconnectedness of genetic, metabolic, and mitochondrial factors observed in diseases such as diabetes, heart failure, neurodegenerative conditions, and viral infections.
Conclusions:
- Mitochondria play a multifaceted role in health and disease, extending beyond energy production.
- Therapeutic advances in metabolic diseases can be achieved by focusing on mitochondrial health and function.
- The convergence of genetic, metabolic, and mitochondrial axes presents a unified view of complex diseases.
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