Our report confirms the link between SLC25A42 and mitochondrial disease in humans, and suggests that pathogenic variants in SLC25A42 should be interpreted with the understanding that the associated phenotype may be highly variable.
A review of PubMed publications was performed from the past 12 months that identified 16 new PMD genes and/or pathogenic variants, and recognition of expanded phenotypes for a wide variety of mitochondrial disease genes.
Here we unveil the first post-translational mechanism regulating CoQ<sub>10</sub> biosynthesis in humans and propose targeting the induction of PPTC7 activity/expression for the treatment of CoQ<sub>10</sub>-related mitochondrial diseases.
Finding the limitations of AOX applicability will help establish the parameters for the future putative use of this enzyme in gene therapies for human mitochondrial diseases.
Biallelic variants in the SPATA5 gene can affect mitochondria in cortical neurons and should be considered in patients with a neurodegenerative disorder and/or with clinical presentation resembling a mitochondrial disorder.
Cerebral folate deficiency (CFD) syndromes are defined as neuro-psychiatric conditions with low CSF folate and attributed to different causes such as autoantibodies against the folate receptor-alpha (FR) protein that can block folate transport across the choroid plexus, FOLR1 gene mutations or mitochondrial disorders.
A neurodegenerative mitochondrial disease phenotype due to biallelic loss-of-function variants in PNPLA8 encoding calcium-independent phospholipase A2γ.
Cerebral folate deficiency (CFD) syndromes are defined as neuro-psychiatric conditions with low CSF folate and attributed to different causes such as autoantibodies against the folate receptor-alpha (FR) protein that can block folate transport across the choroid plexus, FOLR1 gene mutations or mitochondrial disorders.
Only 21 IBA57 mutations have been reported, therefore the phenotypic spectrum of IBA57-related mitochondrial disease has not yet been fully elucidated.
We propose that polyadenylation of structurally and functionally abnormal mitochondrial tRNAs entrains their PNPase/SUV3-mediated destruction, and that this pathway could play an important role in mitochondrial diseases associated with tRNA mutations.
The identification of MRPS2 as an additional gene related to mitochondrial disease further expands the genetic and phenotypic spectra of OXPHOS deficiencies caused by impaired mitochondrial translation.
Moreover, administration of PSG-1 suppressed DOX-induced mitochondrial disorders, which was evidenced by reducing reactive oxygen species, elevating mitochondrial membrane potential and inhibiting the opening of mitochondrial permeability transition pore.
In addition, several metabolic diseases lead to myocardial thickening, either due to intracellular storage (glycogen storage and lysosomal diseases), extracellular deposition (TTR and AL amyloidosis) or due to abnormal energy metabolism (mitochondrial diseases).
Taken together, these data indicate that decreased S6K1 activity in liver is sufficient to delay the neurological and survival defects caused by deficiency of Complex I and suggest that mTOR signaling can modulate mitochondrial disease and metabolism via cell non-autonomous mechanisms.
The discovery of a mitochondrial isoform of ACC1 required for lipoic acid synthesis has intriguing consequences for our understanding of mitochondrial disorders, metabolic regulation of mitochondrial biogenesis and cancer.
Two of these are X-chromosome linked nuclear (nDNA) genes (NDUFA1 and NDUFB11), and 7 are mitochondrial (mtDNA, MT-ND1-6, -4L) genes, which may be responsible for sex-dependent variation in the presentation of mitochondrial diseases.
The discovery of a mitochondrial isoform of ACC1 required for lipoic acid synthesis has intriguing consequences for our understanding of mitochondrial disorders, metabolic regulation of mitochondrial biogenesis and cancer.