Special Issue "Mitochondrial DNA Mutations in Human Diseases"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (15 October 2019).

Special Issue Editor

Prof. Roberto Scatena
E-Mail Website
Guest Editor
Institute of Biochemistry and Clinical Biochemistry. Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome. Università Cattolica del Sacro Cuore, Rome, Italy
Interests: mtDNA; mutations; human diseases; biochemistry; genetics and molecular biology; medicine

Special Issue Information

Dear Colleagues,

Classically, DNA mutations have been considered responsible for a heterogeneous group of inherited mitochondrial diseases, thus limiting their role in human pathophysiology. At present, mitochondria are far more than the “powerhouse” of the cell as they have classically been described.

In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to the redox control of gene expression, and so on. This functional and structural complexity may undergo important derangements to justify the definition of ‘mitochondrial medicine’, which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies that assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury; neurodegenerative diseases; metabolic syndrome; hyperlipidemias; and, above all, cancer, just to mention a few of the most important pathologies.

In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard to their toxicological aspects but, above all, to their potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called “mitoxicants” are well-known from physical, chemical, and biochemical points of view, the often-subtle linkages between drugs and mitochondria is still in need of real pharmacological and therapeutic control at the clinical level.

In this setting, inherited or spontaneous mutations in mtDNA have a fundamental and too-often-neglected role. This lack of consideration often leads to an underestimation of the pathophysiological role of mitochondrial DNA mutations in various human diseases, with important clinical implications in terms of diagnosis and therapy.

We cordially invite researchers working actively in these fields to submit their original research or review manuscripts to this Special Issue on Mitochondrial DNA Mutations in Human Diseases.

Prof. Roberto Scatena
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mtDNA
  • mutations
  • mitochondria
  • human disease
  • therapies

Published Papers (2 papers)

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Research

Open AccessArticle
D-loop Mutations in Renal Cell Carcinoma Improve Predictive Accuracy for Cancer-Related Death by Integrating with Mutations in the NADH Dehydrogenase Subunit 1 Gene
Genes 2019, 10(12), 998; https://doi.org/10.3390/genes10120998 - 02 Dec 2019
Abstract
Renal cell carcinoma (RCC) is associated with various genetic alterations. Although whole-genome/exome sequencing analysis has revealed that nuclear genome alterations are associated with clinical outcomes, the association between nucleotide alterations in the mitochondrial genome and RCC clinical outcomes remains unclear. In this study, [...] Read more.
Renal cell carcinoma (RCC) is associated with various genetic alterations. Although whole-genome/exome sequencing analysis has revealed that nuclear genome alterations are associated with clinical outcomes, the association between nucleotide alterations in the mitochondrial genome and RCC clinical outcomes remains unclear. In this study, we analyzed somatic mutations in the mitochondrial D-loop region, using RCC samples from 61 consecutive patients with localized RCC. Moreover, we analyzed the relationship between D-loop mutations and NADH dehydrogenase subunit 1 (MT-ND1) mutations, which we previously found to be associated with clinical outcomes in localized RCC. Among the 61 localized RCCs, 34 patients (55.7%) had at least one mitochondrial D-loop mutation. The number of D-loop mutations was associated with larger tumor diameter (> 32 mm) and higher nuclear grade (≥ ISUP grade 3). Moreover, patients with D-loop mutations showed no differences in cancer-specific survival when compared with patients without D-loop mutations. However, the co-occurrence of D-loop and MT-ND1 mutations improved the predictive accuracy of cancer-related deaths among our cohort, increasing the concordance index (C-index) from 0.757 to 0.810. Thus, we found that D-loop mutations are associated with adverse pathological features in localized RCC and may improve predictive accuracy for cancer-specific deaths when combined with MT-ND1 mutations. Full article
(This article belongs to the Special Issue Mitochondrial DNA Mutations in Human Diseases)
Open AccessArticle
Maternally Inherited Differences within Mitochondrial Complex I Control Murine Healthspan
Genes 2019, 10(7), 532; https://doi.org/10.3390/genes10070532 - 13 Jul 2019
Abstract
Mitochondrial complex I—the largest enzyme complex of the mitochondrial oxidative phosphorylation machinery—has been proposed to contribute to a variety of age-related pathological alterations as well as longevity. The enzyme complex-consisting proteins are encoded by both nuclear (nDNA) and mitochondrial DNA (mtDNA). While some [...] Read more.
Mitochondrial complex I—the largest enzyme complex of the mitochondrial oxidative phosphorylation machinery—has been proposed to contribute to a variety of age-related pathological alterations as well as longevity. The enzyme complex-consisting proteins are encoded by both nuclear (nDNA) and mitochondrial DNA (mtDNA). While some association studies of mtDNA encoded complex I genes and lifespan in humans have been reported, experimental evidence and the functional consequence of such variants is limited to studies using invertebrate models. Here, we present experimental evidence that a homoplasmic mutation in the mitochondrially encoded complex I gene mt-Nd2 modulates lifespan by altering cellular tryptophan levels and, consequently, ageing-related pathways in mice. A conplastic mouse strain carrying a mutation at m.4738C > A in mt-Nd2 lived slightly, but significantly, shorter than the controls did. The same mutation led to a higher susceptibility to glucose intolerance induced by high-fat diet feeding. These phenotypes were not observed in mice carrying a mutation in another mtDNA encoded complex I gene, mt-Nd5, suggesting the functional relevance of particular mutations in complex I to ageing and age-related diseases. Full article
(This article belongs to the Special Issue Mitochondrial DNA Mutations in Human Diseases)
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