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What is the therapeutic potential of correcting mutations by base editing of the #MitochondrialGenome? This study shows that #mitochondrial #BaseEditing can indeed functionally create & correct mitochondrial pathogenic #mutations in patient-derived cells @PLOSBiology https://plos.io/3ZMa2K2

Correction of m.4291T > C in primary patient-derived fibroblasts. Top left: The primary patient-derived fibroblast line is homoplasmic for the m.4291T > C mutation. Top right: Design of two sets of Left (red) and Right (green) target sequences flanking the spacer region (blue) for TALE-guided editing in MT-TI to correct m.4291C > T (dark red). Mismatched T (red) in TALE target sequence L2. Middle: Overview of the transfection strategy of DdCBE for primary skin fibroblasts. Bottom left: Editing efficiencies of all four combinations Left- and Right-TALE-DdCBE plasmids in primary patient-derived fibroblasts as measured by amplicon sequencing (Illumina NGS). Bottom middle: Ratio of on-target editing vs. bystander editing at any other base within the spacing region in fibroblast cells. Bottom right: Clonal lines of edited primary patient-derived fibroblasts show high variability in mitochondrial heteroplasmy indicating different editing efficiencies per cell (Illumina NGS).

#Fungal infections are hard to treat due to #DrugResistance. @blake_billmyre &co use a high-throughput #TNseq system in #Cryptococcus neoformans to identify >1400 essential genes & reveal a role for #mitochondrial genes in #fluconazole sensitivity @PLOSBiology https://plos.io/4dz3iVm

Schematic of TN-seq in C. neoformans. Top left: Transposon insertions (orange arrow) into nonessential genes results in viable cells. In contrast, insertions into essential genes will result in dead and nonrecoverable cells. Top right: TN-seq works by generating a library of cells where each cell has a single independent transposon insertion in a random location. As in A, those insertions into essential regions cause the cells to die and are nonrecoverable. As a result, the total library (bottom) is depleted in insertions in essential regions. Bottom: The Ac/Ds transposon was split into an Ac transposase and a Ds transposon containing a neomycin resistance marker. This Ds transposon was integrated into an intron of URA5 and the Ac transposase was integrated into the safe haven locus. The resulting stain is ura− and neomycin resistant. Upon initiating transposition via growth on galactose, the strain becomes URA+ and mutant at another locus (depicted here as YFG1).

“Variation of the mitochondrial genome has been also studied as possible source of incomplete penetrance. In fact, constitutive variants defining mtDNA haplogroup J have been found to increase penetrance in families with the m.11778G>A and, more consistently, with the m.14484T>C mutations.” #dna #isogg #mtdna #mitochondrial #haplogroupj

https://onlinelibrary.wiley.com/doi/abs/10.1111/aos.16816

“These findings suggest that elevated Functional Impact (FI) score of mtDNA variants might contribute to premature aging in young adulthood.” #isogg #dna #epigenetics #mtDNA #mitochondrial #biologicalclock

https://pmc.ncbi.nlm.nih.gov/articles/PMC11751369/

SciTech Chronicles. . . . . . . . . . . . . . . . . Jan 16, 2025

https://bit.ly/stc011625

#Antiaging #longevity #LCA #bile #AMPK #liver #AMOC #WHOI #climate #fluxes #proxy-based #British #DNA #Durotriges #Dorset #U5b1 #mitochondrial #Alzheimer’s #Parkinson’s #amyloid #Tau #dopamine #Iceland #Bárðarbunga #eqrthquake #swarm #Holuhraun

“We detailed the genetic, clinical, and molecular profiles of two Han Chinese families with MDD. These families exhibited a range of depression severities and notably low penetrance of MDD. Additionally, distinctive mtDNA polymorphisms associated with haplogroups H2 were identified.” #isogg #dna #mtDNA #mitochondrial #epigenetics #geneadons

https://www.tandfonline.com/doi/full/10.2147/NDT.S465744

#Space Travel Damages #Astronauts At The Cellular Level
#Mitochondrial damage is causing accelerated a#ging in astronauts and could hamper long-term space missions
The report produced by the Guy Foundation, an independent British research foundation, cited multiple causes behind the cellular damage: #radiation and #zerogravity. While residents on the International Space Station exercise constantly to stave off muscle and bone loss, there’s no workout to help your cells.
https://jalopnik.com/space-travel-is-damaging-astronauts-at-the-cellular-lev-1851692078

These findings suggest that elevated FI score of mtDNA variants might contribute to premature aging in young adulthood. (Preprint) #isogg #dna #mitochondrial #mtDNA #haplogroup #aging #geneadons #epigenetics #geneticgenealogy

https://www.researchsquare.com/article/rs-4340944/v1

#Mitochondrial calcium signaling in #pigmentation: @jyotitanwar1993 @MotianiRaj1 &co show that mito Ca2+ uniporter MCU regulates #melanogenesis by activating NFAT2 & Keratin 5; targeting this axis could be used to treat pigmentary disorders #PLOSBiology https://plos.io/4eswpbV

Upregulating #mitochondrial Ca2+ uniporter (MCU) helps #ColorectalCancer cell growth, but what about its regulators? Study shows that MICU2 ensures metabolic flexibility between #glycolysis & #OxPhos and regulates #cancer cell proliferation #PLOSBiology https://plos.io/40pW69s

Our team at #OIST published the first complete #mitochondrial #genome for an #appendicularian #tunicate, #Oikopleura dioica. Its non-coding region is unusually large and repetitive. We plan to sequence more genomes from related species to reveal patterns of evolutionary conservation that will help elucidating function of the unannotated regions. https://doi.org/10.1093/gbe/evae182

New publication from the lab in Methods in Enzymology 📖: A chapter on #massspec based study of #mitochondrial translocation proteins. Free copy available at: https://authors.elsevier.com/a/1jenP_1lc7fPeK

A price for carrying our endosymbiont? Somatic nuclear #mitochondrial DNA (#Numt) insertions arise spontaneously and accumulate in #brain tissues over the human lifespan @ArthurZhou10 @kalpitark @MitoPsychoBio @ryan_e_mills &co #PLOSBiology https://plos.io/3AyrkAq

Cell-to-cell #mitochondrial transfer within the #osteocyte dendritic network regulates #bone tissue homeostasis, but how? This study shows that osteocytes release ADP under stress conditions, triggering mitochondrial transfer #PLOSBiology https://plos.io/3MdO2Ao

Pam16 & Pam18 are essential for #mitochondrial protein import in eukaryotes, but not in #Trypanosomes. @aschneiderlab show that TbPam16/18 have been repurposed to regulate #replication of #maxicircles within the T. brucei mitochondrial genome #PLOSBiology https://plos.io/3STOEis

The human gut microbiome

Influences #health and #disease through metabolic, immune, and neurobehavioral pathways. The composition of #gut #microbiota is affected by diet, drugs, and environment.

Athletes can boost performance by optimizing their gut microbiome, which affects mitochondrial health.

#Fiber, polyphenols, and healthy fats boost #microbiome and #mitochondrial function, while ultra-processed foods harm gut health. Fermented foods and #probiotics can restore it.

#biology