Impaired mitochondrial DNA maintenance in NAFLD: associations between mtDNA copy number, mtDNA damage and BER factors

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is characterized by mitochondrial dysfunction and oxidative stress, potentially compromising mitochondrial DNA (mtDNA) integrity. The contribution of base excision repair (BER) to mtDNA maintenance in NAFLD remains poorly understood. Here, we analyzed mtDNA copy number, mtDNA and nuclear DNA damage, and the expression and mitochondrial protein levels of key BER components in leukocytes from NAFLD patients and healthy controls. NAFLD was associated with increased mtDNA and nuclear DNA damage and reduced mtDNA copy number. Gene expression of the BER-initiating glycosylase NEIL1 and downstream factor APEX1 was decreased, whereas LIG1 was upregulated. Proteomic analysis further revealed lower mitochondrial levels of APEX1, PARP1, FEN1, XRCC1, OGG1 and DNLI3 (encoded by LIG3) in NAFLD. MtDNA copy number positively correlated with BER gene expression, while mtDNA damage showed inverse associations. These results highlight a coordinated impairment of mitochondrial BER in NAFLD, linking defective repair to mtDNA instability and mitochondrial dysfunction.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Peripheral Blood Mononuclear Cell

SUBMITTER: Bianka Swiderska  

LAB HEAD: Sylwia Ziółkowska

PROVIDER: PXD075974 | Pride | 2026-08-17

REPOSITORIES: Pride