A High-Throughput Search for SFXN1 Physical Partners Led to the Identification of ATAD3, HSD10 and TIM50

Tifoun, Nesrine; Bekhouche, Mourad; Heras, José M. De las; Guillaume, Arnaud; Bouleau, Sylvina; Guénal, Isabelle; Mignotte, Bernard; Floch, Nathalie Le

doi:10.3390/biology11091298

Cited by 3 publications

(2 citation statements)

References 66 publications

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“…In the fibroblasts of these patients, the aggregation of mitochondria, the accumulation of mtDNA, and an increase in free cholesterol were observed. These observations by Gunning et al were similar to those associated with ATAD3 cluster deletions reported by Desai et al [34], indicating that the protein resulting from the fusion of the ATAD3A and ATAD3C genes may be nonfunctional.…”

Section: Copy Number Variantssupporting

confidence: 80%

“…Sideroflexin 1 (SFXN1), a human mitochondrial serine transporter, was also shown to interact with ATAD3A in MCF7 cells, a human breast cancer cell line, identified by coimmunoprecipitation followed by shotgun mass spectrometry (coIP-MS) (Figure 2 #6) [34]. The significance of this interaction is yet to be understood.…”

Section: Atad3a-protein Interactions and Functionmentioning

confidence: 99%

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ATAD3A: A Key Regulator of Mitochondria-Associated Diseases

Chen,

Li,

Zambidis

et al. 2023

IJMS

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Mitochondrial membrane protein ATAD3A is a member of the AAA-domain-containing ATPases superfamily. It is important for the maintenance of mitochondrial DNA, structure, and function. In recent years, an increasing number of ATAD3A mutations have been identified in patients with neurological symptoms. Many of these mutations disrupt mitochondrial structure, function, and dynamics and are lethal to patients at a young age. Here, we summarize the current understanding of the relationship between ATAD3A and mitochondria, including the interaction of ATAD3A with mitochondrial DNA and mitochondrial/ER proteins, the regulation of ATAD3A in cholesterol mitochondrial trafficking, and the effect of known ATAD3A mutations on mitochondrial function. In the current review, we revealed that the oligomerization and interaction of ATAD3A with other mitochondrial/ER proteins are vital for its various functions. Despite affecting different domains of the protein, nearly all documented mutations observed in ATAD3A exhibit either loss-of-function or dominant-negative effects, potentially leading to disruption in the dimerization of ATAD3A; autophagy; mitophagy; alteration in mitochondrial number, size, and cristae morphology; and diminished activity of mitochondrial respiratory chain complexes I, IV, and V. These findings imply that ATAD3A plays a critical role in mitochondrial dynamics, which can be readily perturbed by ATAD3A mutation variants.

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Section: Copy Number Variantssupporting

confidence: 80%

Section: Atad3a-protein Interactions and Functionmentioning

confidence: 99%

ATAD3A: A Key Regulator of Mitochondria-Associated Diseases

Chen,

Li,

Zambidis

et al. 2023

IJMS

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Distinct CSF biomarker-associated DNA methylation in Alzheimer’s disease and cognitively normal subjects

et al. 2023

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Background Growing evidence has demonstrated that DNA methylation (DNAm) plays an important role in Alzheimer’s disease (AD) and that DNAm differences can be detected in the blood of AD subjects. Most studies have correlated blood DNAm with the clinical diagnosis of AD in living individuals. However, as the pathophysiological process of AD can begin many years before the onset of clinical symptoms, there is often disagreement between neuropathology in the brain and clinical phenotypes. Therefore, blood DNAm associated with AD neuropathology, rather than with clinical data, would provide more relevant information on AD pathogenesis. Methods We performed a comprehensive analysis to identify blood DNAm associated with cerebrospinal fluid (CSF) pathological biomarkers for AD. Our study included matched samples of whole blood DNA methylation, CSF Aβ42, phosphorylated tau181 (pTau181), and total tau (tTau) biomarkers data, measured on the same subjects and at the same clinical visits from a total of 202 subjects (123 CN or cognitively normal, 79 AD) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. To validate our findings, we also examined the association between premortem blood DNAm and postmortem brain neuropathology measured on a group of 69 subjects in the London dataset. Results We identified a number of novel associations between blood DNAm and CSF biomarkers, demonstrating that changes in pathological processes in the CSF are reflected in the blood epigenome. Overall, the CSF biomarker-associated DNAm is relatively distinct in CN and AD subjects, highlighting the importance of analyzing omics data measured on cognitively normal subjects (which includes preclinical AD subjects) to identify diagnostic biomarkers, and considering disease stages in the development and testing of AD treatment strategies. Moreover, our analysis revealed biological processes associated with early brain impairment relevant to AD are marked by DNAm in the blood, and blood DNAm at several CpGs in the DMR on HOXA5 gene are associated with pTau181 in the CSF, as well as tau-pathology and DNAm in the brain, nominating DNAm at this locus as a promising candidate AD biomarker. Conclusions Our study provides a valuable resource for future mechanistic and biomarker studies of DNAm in AD.

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Distinct CSF biomarker-associated DNA methylation in Alzheimer's disease and cognitively normal subjects

Zhang

Young

Gomez

et al. 2023

Preprint

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Background Growing evidence has demonstrated that DNA methylation (DNAm) plays an important role in Alzheimer's disease (AD) and that DNAm differences can be detected in the blood of AD subjects. Most studies have correlated blood DNAm with the clinical diagnosis of AD in living individuals. However, as the pathophysiological process of AD can begin many years before the onset of clinical symptoms, there is often disagreement between neuropathology in the brain and clinical phenotypes. Therefore, blood DNAm associated with AD neuropathology, rather than with clinical data, would provide more relevant information on AD pathogenesis. Methods We performed a comprehensive analysis to identify blood DNAm associated with cerebrospinal fluid (CSF) pathological biomarkers for AD. Our study included matched samples of whole blood DNA methylation, CSF Aβ42, phosphorylated tau181 (pTau181), and total tau (tTau) biomarkers data, measured on the same subjects and at the same clinical visits from a total of 202 subjects (123 CN or cognitively normal, 79 AD) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. To validate our findings, we also examined the association between premortem blood DNAm and postmortem brain neuropathology measured on a group of 69 subjects in the London dataset. Results We identified a number of novel associations between blood DNAm and CSF biomarkers, demonstrating that changes in pathological processes in the CSF are reflected in the blood epigenome. Overall, the CSF biomarker-associated DNAm is relatively distinct in CN and AD subjects, highlighting the importance of analyzing omics data measured on cognitively normal subjects (which includes preclinical AD subjects) to identify diagnostic biomarkers, and considering disease stages in the development and testing of AD treatment strategies. Moreover, our analysis revealed biological processes associated with early brain impairment relevant to AD are marked by DNAm in the blood, and blood DNAm at several CpGs in the DMR on HOXA5 gene are associated with pTau181 in the CSF, as well as tau-pathology and DNAm in the brain, nominating DNAm at this locus as a promising candidate AD biomarker. Conclusions Our study provides a valuable resource for future mechanistic and biomarker studies of DNAm in AD.

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A High-Throughput Search for SFXN1 Physical Partners Led to the Identification of ATAD3, HSD10 and TIM50

Cited by 3 publications

References 66 publications

ATAD3A: A Key Regulator of Mitochondria-Associated Diseases

ATAD3A: A Key Regulator of Mitochondria-Associated Diseases

Distinct CSF biomarker-associated DNA methylation in Alzheimer’s disease and cognitively normal subjects

Distinct CSF biomarker-associated DNA methylation in Alzheimer's disease and cognitively normal subjects

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