Human Mitochondrial Protein HSPD1 Binds to and Regulates the Repair of Deoxyinosine in DNA

Abstract

The generation of deoxyinosine (dI) in DNA is one of the most important sources of genetic mutations, which may lead to cancer and other human diseases. A further understanding of the biological consequences of dI necessitates the identification and functional characterizations of dI-binding proteins. Herein, we employed a mass spectrometry-based proteomics approach to detect the cellular proteins that may sense the presence of dI in DNA. Our results demonstrated that human mitochondrial heat shock protein 60 (HSPD1) can interact with dI-bearing DNA. We further demonstrated the involvement of HSPD1 in the sodium nitrite-induced DNA damage response and in the modulation of dI levels in vitro and in human cells. Together, these findings revealed HSPD1 as a novel dI-binding protein that may play an important role in the mitochondrial DNA damage control in human cells.

Protective impacts of mitochondria enhancers against thermal stress in poultry

“…Broilers exposed to HS also had lower ATP levels than the control group, as reported by Zhang et al (2018a) . Additionally, Zheng et al (2023) found a positive correlation between ATP levels and mitochondrial DNA ( mtDNA ) number, resulting from mitochondrial dysfunction in the liver. The final stage of the mitochondrial respiration chain involves cyclooxygenase ( COX ) and Cyt-c and impacts the generation of ATP and ROS and their elimination ( Sena and Chandel, 2012 ).…”

“…The 37 genes in mitochondrial DNA are all essential for regular mitochondrial function, and studies have displayed that mitochondrial dysfunction is accompanied by reduced mtDNA quality ( Zheng et al, 2023 ). This suggests that mitochondrial dysfunction may be a potential reason for the reduced growth performance and feed efficiency detected in heat-stressed broilers ( Chen et al, 2023a ).…”

“…This suggests that mitochondrial dysfunction may be a potential reason for the reduced growth performance and feed efficiency detected in heat-stressed broilers ( Chen et al, 2023a ). Heat stress can induce oxidative stress in mtDNA ( Chen et al, 2023b ), reducing mitochondrial efficiency and repeated ROS eruptions, further aggravating mitochondrial dysfunction ( Zheng et al, 2023 ). Therefore, mtDNA changes are the main mechanism of mitochondrial dysfunction ( Chen et al, 2023b ).…”

ICLAMP: a novel technique to explore adenosine deamination via inosine chemical labeling and affinity molecular purification

“…Inosine, as the deaminated adenosine, leads to A‐to‐G transitions within the DNA sequence, which may accelerate cancer development [21,22]. Notably, hypoxanthine, the nucleobase for deoxyinosine, has been detected as a spontaneous DNA deamination product [23,24].…”

“…To decipher the complexities of gene regulation on the genomic DNA and transcribed RNA, and its impact on human diseases, a new technique is required to identify and analyze such hidden base editing mechanisms. Inosine, as the deaminated adenosine, leads to Ato-G transitions within the DNA sequence, which may accelerate cancer development [21,22]. Notably, hypoxanthine, the nucleobase for deoxyinosine, has been detected as a spontaneous DNA deamination product [23,24].…”