Abstracto

Chronic kidney illness, acute kidney damage, and mitochondrial cytopathies of the renal system all include mitochondrial DNA-mediated inflammation

Griffith Gilbert

Adenosine triphosphate synthesis, metabolic control, the formation of reactive oxygen species, the preservation of intracellular calcium homeostasis, and the management of apoptosis are only a few of the important functions performed by mitochondria, which are key intracellular organelles. Both healthy and pathological situations frequently result in the change of mitochondria. The function of mitochondria in the kidneys is directly tied to their form and structure, and illnesses associated with mitochondrial malfunction have been found. “Mitochondrial cytopathies” refer to illnesses caused by mitochondrial malfunction. Evidence suggests that the two primary paths of end-stage renal disease, chronic kidney disease (CKD), and acute kidney injury, include mitochondrial dysfunction in their aetiology (AKI). Kidney mitochondrial cytopathies primarily present as cystic kidney disorders, localised segmental glomerular sclerosis, and tubular abnormalities. Mutations in the mtDNA and nDNA genes are responsible for the problems. Because the proximal tubular cells are more susceptible to oxidative stress, they are more likely to develop respiratory chain abnormalities, which can result in low-molecular-weight proteins or an electrolyte loss. Myoclonic epilepsy, ragged red muscle fibres (MERRF), and Pearson’s, Kearns-Sayre, and Leigh syndromes are common in patients with mitochondrial tubulopathy. The bulk of mtDNA fragment deletions found in these disorders are genetic mutations. Studies have demonstrated the close relationship between mitochondrial dysfunction and the development of CKD by demonstrating significantly increased ROS production, upregulation of COX I and IV expression, and inactivation of complex IV in peripheral blood mononuclear cells of patients with stage IV-V CKD. With the ultimate objective of finding mitochondrial targets to enhance therapy of patients with chronic renal illnesses, it is also explored how cellular signals and demands translate into mitochondrial remodelling and cellular damage, including the impact of microRNAs and lncRNAs [1].

For healthy kidney physiology, mitochondria’s integrity and functionality are crucial. Since its anomalies have the potential to impair aerobic respiration, cause cellular malfunction, and even cause cell death, mitochondrial DNA (mtDNA) has received a great deal of attention in recent years. Urinary mtDNA-CN has the potential to be a useful marker for clinical diagnosis and evaluation of kidney function. In particular, aberrant mtDNA copy number (mtDNA-CN) is related with the onset of acute renal damage and chronic kidney disease. According to a number of lines of research, mtDNA may also activate innate immunity, causing inflammation and fibrosis in the kidneys. Under conditions of cell stress, mtDNA can be released into the cytoplasm and detected by a variety of DNA-sensing systems, such as Toll-like receptor 9 (TLR9), cytosolic cGAS-stimulator of interferon genes (STING) signalling, and inflammasome activation. These systems then control subsequent inflammatory cascades. The characteristics of these mtDNA-sensing pathways mediating inflammatory responses are outlined in this review, along with their significance in the pathophysiology of acute kidney injury, nondiabetic chronic kidney disease, and diabetic kidney disease. We also emphasise the unique treatment target for these kidney disorders, mtDNA-mediated inflammatory pathways [2].