Molecular Research on Mitochondrial Dysfunction

This Special Issue collects current knowledge on the molecular mechanisms underlying mitochondrial dysfunction and its related diseases, as well as therapies and perspectives pertaining to their treatment [...].


of 3
Although mtDNA replication, transcription and translation occur contextually, microscopy and biochemical approaches revealed the presence of nucleic acid-protein aggregates that likely host mtDNA-or mtRNA-related processes [9][10][11]. In this Special Issue, Xavier and colleagues discuss the different putative non-membranous compartmentalization of mtDNA-and mtRNA-containing granules and their protein composition [12]. mtDNA release, it is necessary to better understand how mtDNA is organized in nucleoids, how nucleoid stability is controlled, and whether mtDNA and mtRNA release are independent or linked. Although mtDNA replication, transcription and translation occur contextually, microscopy and biochemical approaches revealed the presence of nucleic acid-protein aggregates that likely host mtDNA-or mtRNA-related processes [9][10][11]. In this Special Issue, Xavier and colleagues discuss the different putative non-membranous compartmentalization of mtDNA-and mtRNA-containing granules and their protein composition [12]. A limiting factor in developing new therapies for mitochondrial diseases has been the substantial lack and/or inappropriateness of suitable models. Mouse models have been, and still are, central in this process; however, they often fail to recapitulate the clinical features of human syndromes, even in the presence of the biochemical and molecular hallmarks. However, the introduction of induced pluripotent stem cells (iPSCs) has changed this paradigm, as discussed by McKnight and colleagues [13]. Interestingly, the authors also underscore some limitations in the use of iPSCs, including the challenges related to their maintenance and differentiation, and the intrinsic difficulties in using differentiated cells for drug-screening.
Despite the many difficulties in developing therapies for mitochondrial diseases, some important milestones have been reached, as discussed by Ramòn and colleagues [5]. These authors focused on mtDNA maintenance defects; these are a highly relevant group of mitochondrial diseases resulting from mutations in genes that encode components of the replication/transcription machinery, of nucleotide metabolism, and of mitochondrial dynamics. Several approaches have been tested over the last 10 years, including direct scavenging of toxic metabolites, enzyme-replacement therapy, hematopoietic stem-cell transplantation, liver transplantation, the administration of deoxyribonucleotides, and gene therapy. Additionally, metabolic reprogramming may be exploited to improve mitochondrial functions in some cancers by exploiting melatonin, an endogenous compound that is able to shift the metabolism from glycolysis to OXPHOS, as discussed by Reiter and colleagues [14].
Although research on the topic is still in its infancy, the possibility of having a cure for at least some mitochondrial diseases and diseases with mitochondrial alterations finally seems to be looming.
Funding: This editorial received no external funding.

Conflicts of Interest:
The authors declare no conflict of interest. A limiting factor in developing new therapies for mitochondrial diseases has been the substantial lack and/or inappropriateness of suitable models. Mouse models have been, and still are, central in this process; however, they often fail to recapitulate the clinical features of human syndromes, even in the presence of the biochemical and molecular hallmarks. However, the introduction of induced pluripotent stem cells (iPSCs) has changed this paradigm, as discussed by McKnight and colleagues [13]. Interestingly, the authors also underscore some limitations in the use of iPSCs, including the challenges related to their maintenance and differentiation, and the intrinsic difficulties in using differentiated cells for drug-screening.
Despite the many difficulties in developing therapies for mitochondrial diseases, some important milestones have been reached, as discussed by Ramòn and colleagues [5]. These authors focused on mtDNA maintenance defects; these are a highly relevant group of mitochondrial diseases resulting from mutations in genes that encode components of the replication/transcription machinery, of nucleotide metabolism, and of mitochondrial dynamics. Several approaches have been tested over the last 10 years, including direct scavenging of toxic metabolites, enzyme-replacement therapy, hematopoietic stem-cell transplantation, liver transplantation, the administration of deoxyribonucleotides, and gene therapy. Additionally, metabolic reprogramming may be exploited to improve mitochondrial functions in some cancers by exploiting melatonin, an endogenous compound that is able to shift the metabolism from glycolysis to OXPHOS, as discussed by Reiter and colleagues [14].
Although research on the topic is still in its infancy, the possibility of having a cure for at least some mitochondrial diseases and diseases with mitochondrial alterations finally seems to be looming.
Funding: This editorial received no external funding.