Frequency and association of mitochondrial genetic variants with neurological disorders

Cruz, Ana Carolina Pinto da; Ferrasa, Adriano; Muotri, Alysson R.; Herai, Roberto H.

doi:10.1016/j.mito.2018.09.005

Cited by 25 publications

(11 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CNVs in specific regions on the chromosome (12, 19, 20, and 21) are associated with ASD, 69 , 70 although no such variations are found in the mt D-Loop of autism patients. 71 The ratios of mt-DNA for all three genes (ND1, CytB, and ND4) to nuclear DNA were increased in the frontal cortex of autistic subjects compared with the controls. Moreover, the ratio of the mitochondrial genes ND1, ND4 and CytB to pyruvate kinase was significantly higher in autistic individuals as compared to controls.…”

Section: Complexes Dysfunction Of Mitochondrion Coded Genes In Autistic Disordermentioning

confidence: 88%

Mitochondrial dysfunction: A hidden trigger of autism?

et al. 2021

View full text Add to dashboard Cite

Autism is a heterogeneous neurodevelopmental and neuropsychiatric disorder with no precise etiology. Deficits in cognitive functions uncover at early stages and are known to have an environmental and genetic basis. Since autism is multifaceted and also linked with other comorbidities associated with various organs, there is a possibility that there may be a fundamental cellular process responsible for this. These reasons place mitochondria at the point of interest as it is involved in multiple cellular processes predominantly involving metabolism. Mitochondria encoded genes were taken into consideration lately because it is inherited maternally, has its own genome and also functions the time of embryo development. Various researches have linked mitochondrial mishaps like oxidative stress, ROS production and mt-DNA copy number variations to autism. Despite dramatic advances in autism research worldwide, the studies focusing on mitochondrial dysfunction in autism is rather minimal, especially in India. India, owing to its rich diversity, may be able to contribute significantly to autism research. It is vital to urge more studies in this domain as it may help to completely understand the basics of the condition apart from a genetic standpoint. This review focuses on the worldwide and Indian scenario of autism research; mitochondrial abnormalities in autism and possible therapeutic approaches to combat it.

show abstract

Section: Complexes Dysfunction Of Mitochondrion Coded Genes In Autistic Disordermentioning

confidence: 88%

Mitochondrial dysfunction: A hidden trigger of autism?

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Neurons contain a high number of mitochondria, depend on these organelles for energy production, and are particularly vulnerable to the accumulation of mtDNA mutations with aging, that can expand to heteroplasmic levels causing respiratory chain dysfunction (5). Indeed, single nucleotide polymorphisms, deletions, insertions, and copy number variations of the mtDNA have been linked to the occurrence of neurological disorders, including neurodegenerative ones (6, 7).…”

Section: Introductionmentioning

confidence: 99%

Mitoepigenetics and Neurodegenerative Diseases

Coppedè

Stoccoro

2019

Front. Endocrinol.

View full text Add to dashboard Cite

Mitochondrial impairment and increased oxidative stress are common features in neurodegenerative disorders, leading researchers to speculate that epigenetic changes in the mitochondrial DNA (mitoepigenetics) could contribute to neurodegeneration. The few studies performed so far to address this issue revealed impaired methylation levels of the mitochondrial regulatory region (D-loop region) in both animal models, postmortem brain regions, or circulating blood cells of patients with Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Those studies also revealed that mtDNA D-loop methylation levels are subjected to a dynamic regulation within the progression of the neurodegenerative process, could be affected by certain neurodegenerative disease-causative mutations, and are inversely correlated with the mtDNA copy number. The methylation levels of other mtDNA regions than the D-loop have been scarcely investigated in human specimens from patients with neurodegenerative disorders or in animal models of the disease, and evidence of impaired methylation levels is often limited to a single study, making it difficult to clarify their correlation with mitochondrial dynamics and gene expression levels in these disorders. Overall, the preliminary results of the studies performed so far are encouraging making mitoepigenetics a timely and attractive field of investigation, but additional research is warranted to clarify the connections among epigenetic changes occurring in the mitochondrial genome, mitochondrial DNA dynamics and gene expression, and the neurodegenerative process.

show abstract

“…The advent of "omics" sciences and the development of specific bioinformatics algorithms gave systematics to analyses involving mtDNA and its linkage to related diseases [75]. Among disorders already known to be determined by mtDNA variants [76], the best characterized are oxidative stress induced ones, such as Alzheimer's, Parkinson's and other neurodegenerative disorders [77].…”

Section: Discussionmentioning

confidence: 99%

Possible A2E Mutagenic Effects on RPE Mitochondrial DNA from Innovative RNA-Seq Bioinformatics Pipeline

et al. 2020

View full text Add to dashboard Cite

Mitochondria are subject to continuous oxidative stress stimuli that, over time, can impair their genome and lead to several pathologies, like retinal degenerations. Our main purpose was the identification of mtDNA variants that might be induced by intense oxidative stress determined by N-retinylidene-N-retinylethanolamine (A2E), together with molecular pathways involving the genes carrying them, possibly linked to retinal degeneration. We performed a variant analysis comparison between transcriptome profiles of human retinal pigment epithelial (RPE) cells exposed to A2E and untreated ones, hypothesizing that it might act as a mutagenic compound towards mtDNA. To optimize analysis, we proposed an integrated approach that foresaw the complementary use of the most recent algorithms applied to mtDNA data, characterized by a mixed output coming from several tools and databases. An increased number of variants emerged following treatment. Variants mainly occurred within mtDNA coding sequences, corresponding with either the polypeptide-encoding genes or the RNA. Time-dependent impairments foresaw the involvement of all oxidative phosphorylation complexes, suggesting a serious damage to adenosine triphosphate (ATP) biosynthesis, that can result in cell death. The obtained results could be incorporated into clinical diagnostic settings, as they are hypothesized to modulate the phenotypic expression of mtDNA pathogenic variants, drastically improving the field of precision molecular medicine.

show abstract

Frequency and association of mitochondrial genetic variants with neurological disorders

Cited by 25 publications

References 143 publications

Mitochondrial dysfunction: A hidden trigger of autism?

Mitochondrial dysfunction: A hidden trigger of autism?

Mitoepigenetics and Neurodegenerative Diseases

Possible A2E Mutagenic Effects on RPE Mitochondrial DNA from Innovative RNA-Seq Bioinformatics Pipeline

Contact Info

Product

Resources

About