Mitochondrial Dysfunction Associated with mtDNA in Metabolic Syndrome and Obesity

Metabolic syndrome (MetS) is a precursor to the major health diseases associated with high mortality in industrialized countries: cardiovascular disease and diabetes. An important component of the pathogenesis of the metabolic syndrome is mitochondrial dysfunction, which is associated with tissue hypoxia, disruption of mitochondrial integrity, increased production of reactive oxygen species, and a decrease in ATP, leading to a chronic inflammatory state that affects tissues and organ systems. The mitochondrial AAA + protease Lon (Lonp1) has a broad spectrum of activities. In addition to its classical function (degradation of misfolded or damaged proteins), enzymatic activity (proteolysis, chaperone activity, mitochondrial DNA (mtDNA)binding) has been demonstrated. At the same time, the spectrum of Lonp1 activity extends to the regulation of cellular processes inside mitochondria, as well as outside mitochondria (nuclear localization). This mitochondrial protease with enzymatic activity may be a promising molecular target for the development of targeted therapy for MetS and its components. The aim of this review is to elucidate the role of mtDNA in the pathogenesis of metabolic syndrome and its components as a key component of mitochondrial dysfunction and to describe the promising and little-studied AAA + LonP1 protease as a potential target in metabolic disorders.

Automated summary

Metabolic syndrome acts as a precursor to major health diseases such as cardiovascular disease and diabetes, which have high mortality rates in industrialized countries. Mitochondrial dysfunction plays a crucial role in the pathogenesis of metabolic syndrome, leading to tissue hypoxia, disruption of mitochondrial integrity, increased production of reactive oxygen species, and decreased ATP levels, resulting in chronic inflammation affecting tissues and organs. The mitochondrial protease Lon (Lonp1) shows potential as a molecular target for the development of targeted therapy for metabolic syndrome and its components due to its broad spectrum of activities, including protein degradation, chaperone activity, and mitochondrial DNA binding.