Genetic basis of mitochondrial diseases

Gusic, Mirjana

doi:10.1002/1873-3468.14068

Cited by 30 publications

(19 citation statements)

References 285 publications

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“…New sequencing platforms have revolutionized diagnostics of such diseases, mainly exome and wholegenome approaches, including mitochondrial heteroplasmy [33]. Nevertheless, a holistic -omics approach is needed to generate more comprehensive results, also requiring new bioinformatics tools to properly analyze them [34][35][36][37][38].…”

Section: Structural Genomicsmentioning

confidence: 99%

“…Interestingly, non-coding sequences may be linked to some diseases [32]. As with structural genomics, organelle transcriptomics and mitochondrial disorders are also related to non-coding RNA [37]. Recently, TGS has allowed the sequencing of a class of them known as circular RNA (circRNA), which was previously refractory to sequencing [124].…”

Section: Functional Genomicsmentioning

confidence: 99%

“…Besides, as with genomics and transcriptomics, mitochondrial diseases have also been linked to organelle epigenetics [37]. Likewise, it is possible to study epigenomes of organisms, tissues, cells and cellular compartments and organelles such as nuclei, mitochondria and chloroplasts.…”

Section: Epigenomicsmentioning

confidence: 99%

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Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

et al. 2021

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Recent developments have revolutionized the study of biomolecules. Among them are molecular markers, amplification and sequencing of nucleic acids. The latter is classified into three generations. The first allows to sequence small DNA fragments. The second one increases throughput, reducing turnaround and pricing, and is therefore more convenient to sequence full genomes and transcriptomes. The third generation is currently pushing technology to its limits, being able to sequence single molecules, without previous amplification, which was previously impossible. Besides, this represents a new revolution, allowing researchers to directly sequence RNA without previous retrotranscription. These technologies are having a significant impact on different areas, such as medicine, agronomy, ecology and biotechnology. Additionally, the study of biomolecules is revealing interesting evolutionary information. That includes deciphering what makes us human, including phenomena like non-coding RNA expansion. All this is redefining the concept of gene and transcript. Basic analyses and applications are now facilitated with new genome editing tools, such as CRISPR. All these developments, in general, and nucleic-acid sequencing, in particular, are opening a new exciting era of biomolecule analyses and applications, including personalized medicine, and diagnosis and prevention of diseases for humans and other animals.

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Section: Structural Genomicsmentioning

confidence: 99%

Section: Functional Genomicsmentioning

confidence: 99%

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Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

et al. 2021

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“…A significant number of reports on pathogenic mutations of mtDNA have been accumulating in the last three decades, in association with a wide spectrum of clinical presentations [ 1 , 53 , 54 , 55 ]. Despite the impressive number of disease-related mutations identified in recent years [ 56 ], new pathogenic mutations continue to be reported ( ) (las access 20 December 2021). For instance, a constellation of mutations in the seven ND genes encoded by mtDNA is responsible for a substantial fraction of isolated defects of CI [ 56 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Neurodegeneration

Zeviani

Viscomi

2022

Cells

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Mitochondria are cytoplasmic organelles, which generate energy as heat and ATP, the universal energy currency of the cell. This process is carried out by coupling electron stripping through oxidation of nutrient substrates with the formation of a proton-based electrochemical gradient across the inner mitochondrial membrane. Controlled dissipation of the gradient can lead to production of heat as well as ATP, via ADP phosphorylation. This process is known as oxidative phosphorylation, and is carried out by four multiheteromeric complexes (from I to IV) of the mitochondrial respiratory chain, carrying out the electron flow whose energy is stored as a proton-based electrochemical gradient. This gradient sustains a second reaction, operated by the mitochondrial ATP synthase, or complex V, which condensates ADP and Pi into ATP. Four complexes (CI, CIII, CIV, and CV) are composed of proteins encoded by genes present in two separate compartments: the nuclear genome and a small circular DNA found in mitochondria themselves, and are termed mitochondrial DNA (mtDNA). Mutations striking either genome can lead to mitochondrial impairment, determining infantile, childhood or adult neurodegeneration. Mitochondrial disorders are complex neurological syndromes, and are often part of a multisystem disorder. In this paper, we divide the diseases into those caused by mtDNA defects and those that are due to mutations involving nuclear genes; from a clinical point of view, we discuss pediatric disorders in comparison to juvenile or adult-onset conditions. The complementary genetic contributions controlling organellar function and the complexity of the biochemical pathways present in the mitochondria justify the extreme genetic and phenotypic heterogeneity of this new area of inborn errors of metabolism known as ‘mitochondrial medicine’.

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“…In addition, this example also shows how important the new technical approaches are to define the genetic cause of mitochondrial disorders in patients. Along these lines, the article by Gusic et al highlights the genetics underlying mitochondrial disorders [14].…”

mentioning

confidence: 99%