Aspartate β-hydroxylase disrupts mitochondrial DNA stability and function in hepatocellular carcinoma

• DOI: 10.1038/oncsis.2017.64
• Publication Date: 2017-07-17T13:20:42Z
• Authors: C Tang; Y Hou; H Wang; K Wang; H Xiang; X Wan; Y Xia; J Li; W Wei; S Xu; Z Lei; T M Pawlik; H Wang; M Wu; F Shen
• Keywords: TFAM

The mechanism of aberrant mitochondrial genome and function in hepatocellular carcinoma (HCC) remains largely unknown. Our previous study demonstrated an increased expression aspartate β-hydroxylase (ASPH) HCC tissues, which was associated with tumor invasiveness a worse prognosis. Currently, we unexpectedly observed the presence ASPH purified protein fraction. In addition, immunostaining both exogenously endogenously expressed showed colocalization biomarkers. This aimed to investigate whether is involved malfunction HCC. results that overexpression tissues correlated decreased copy numbers displacement loop (D-loop) NADH dehydrogenase subunit 1 (ND-1) enhanced D-loop mutation, suggesting disrupted DNA (mtDNA) stability. reduced mtDNA were aggressive clinicopathological features loss integrity induced by enforced accompanied dysfunction, characterized membrane potential, ATP generation reactive oxygen species. contrast, knocking down siRNA cell lines opposite impact on function. Mass spectrometry co-immunoprecipitation further identified interacted histone H2A member X (H2AX). diminished interaction between H2AX transcription factor A (mtTFA), important DNA-binding for replication, then binding mtTFA region. Collectively, our demonstrate disrupts through H2AX-mtTFA signal, thereby affecting functions