Work

Faculty Opinions recommendation of Mitochondrial damage and activation of the STING pathway lead to renal inflammation and fibrosis.

Year: 2019

Type: peer-review

Abstract: Fibrosis of the kidney is the final common pathway leading to end stage renal failure.By analyzing kidneys of patients and animal models with fibrosis we observed a significant mitochondrial defect, including the loss of the mitochondrial transcription factor A (TFAM) in kidney tubule cells.Here, we generated mice with tubule-specific deletion of TFAM (Ksp-Cre/ Tfam flox/flox ).While these mice developed severe mitochondrial loss and energetic deficit (ATP level decline) by 6 weeks of age, kidney fibrosis, immune cell infiltration and progressive azotemia causing death was only observed around 12 weeks of age.Mechanistic studies demonstrated that in the TFAM KO mice aberrant packaging of the mitochondrial DNA (mtDNA) resulted in escape of the mtDNA into the cytosol of the renal cells, activation of the cytosolic cGAS-STING (Stimulator of interferon genes) DNA sensing pathway, and thus cytokine

Source: Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

DOI: 10.3410/f.736512311.793565971

Author: Navdeep Chandel

Institution: Northwestern University

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: American Diabetes Association, National Institute of Diabetes and Digestive and Kidney Diseases