Loss of an uncharacterized mitochondrial methionine tRNA-synthetase induces mitochondrial unfolded protein response in Caenorhabditis elegans DOI Creative Commons
Bharat Vivan Thapa, Mohit Das, James P Held

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Aminoacyl-tRNA synthetases (aaRSs) are essential for translation, as they charge tRNA molecules with their corresponding amino acids. Alterations in aaRSs can significantly disrupt both cytosolic and mitochondrial translation. Through a forward genetic screen unfolded protein response (UPR mt ) activators C. elegans , we identified missense mutation (P447V) the previously uncharacterized gene Y105E8A.20, which encodes dually localized methionine synthetase (MetRS). Here, characterize UPR induction by call mars-2 demonstrate that P447V allele is loss-of-function mutation. Furthermore, show impaired activity mitochondria triggers . This strain provides valuable tool studying translation understanding how involved homeostasis.

Язык: Английский

Interaction and regulation of the mitochondrial proteome – in health and disease DOI Creative Commons
Johan Palmfeldt

Expert Review of Proteomics, Год журнала: 2025, Номер 22(1), С. 19 - 33

Опубликована: Янв. 2, 2025

Introduction Mitochondria contain multiple pathways including energy metabolism and several signaling synthetic pathways. Mitochondrial proteomics is highly valuable for studying diseases inherited metabolic disorders, complex common disorders like neurodegeneration, diabetes cancer, since they all to some degree have mitochondrial underpinnings.

Язык: Английский

Процитировано

0
The Role of mtDNA Mutations in Atherosclerosis: The Influence of Mitochondrial Dysfunction on Macrophage Polarization DOI Open Access
Evgeniya I. Fedotova, Alexey V. Berezhnov, Daniil Y. Popov

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1019 - 1019

Опубликована: Янв. 25, 2025

Atherosclerosis is a complex inflammatory process associated with high-mortality cardiovascular diseases. Today, there growing body of evidence linking atherosclerosis to mutations mitochondrial DNA (mtDNA). But the mechanism this link insufficiently studied. progression involves different cell types and macrophages are one most important. Due their high plasticity, can demonstrate pro-inflammatory pro-atherogenic (macrophage type M1) or anti-inflammatory anti-atherogenic M2) effects. These two types, formed as result external stimuli, differ significantly in metabolic profile, which suggests central role mitochondria implementation macrophage polarization route. According this, we assume that mtDNA causing disturbances play an internal trigger, leading formation M1 M2. This review provides comparative analysis characteristics function possible associations linked inflammation-based pathologies including atherosclerosis.

Язык: Английский

Процитировано

0
FAM43A coordinates mtDNA replication and mitochondrial biogenesis in response to mtDNA depletion DOI
Alva G. Sainz,

Gladys R. Rojas,

Alexandra G Moyzis

и другие.

The Journal of Cell Biology, Год журнала: 2025, Номер 224(3)

Опубликована: Янв. 27, 2025

Mitochondrial retrograde signaling (MRS) pathways relay the functional status of mitochondria to elicit homeostatic or adaptive changes in nuclear gene expression. Budding yeast have “intergenomic signaling” that sense amount mitochondrial DNA (mtDNA) independently oxidative phosphorylation (OXPHOS), primary function genes encoded by mtDNA. However, MRS mtDNA mammalian cells remain poorly understood. We found mtDNA-depleted IMR90 can sustain OXPHOS for a significant time, providing robust model system interrogate human intergenomic signaling. identified FAM43A, largely uncharacterized protein, as CHK2-dependent early responder depletion. Depletion FAM43A activates biogenesis program, resulting an increase mass and copy number via CHK2-mediated upregulation p53R2 form ribonucleotide reductase. propose performs checkpoint-like limit turnover under conditions depletion replication stress.

Язык: Английский

Процитировано

0
A Quantitative Approach to Mapping Mitochondrial Specialization and Plasticity DOI Creative Commons
Anna S. Monzel,

Jack Devine,

Darshana Kapri

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Abstract Mitochondria are a diverse family of organelles that specialize to accomplish complimentary functions 1–3 . All mitochondria share general features, but not all created equal 4 .Here we develop quantitative pipeline define the degree molecular specialization among different mitochondrial phenotypes – or mitotypes By distilling hundreds validated genes/proteins into 149 biologically interpretable MitoPathway scores (MitoCarta 3.0 5 ) simple mitotyping allows investigators quantify and interpret diversity plasticity from transcriptomics proteomics data across variety natural experimental contexts. We show mouse human multi-organ segregate along two main axes specialization, contrasting anabolic (liver) catabolic (brain) tissues. In cultured primary fibroblasts exhibiting robust time-dependent treatment-induced metabolic 6–8 , demonstrate how mitotype given cell type recalibrates i) over time in parallel with hallmarks aging, ii) response genetic, pharmacological, perturbations. Investigators can now use MitotypeExplorer.org associated code visualize, multivariate space biology.

Язык: Английский

Процитировано

0
Loss of an uncharacterized mitochondrial methionine tRNA-synthetase induces mitochondrial unfolded protein response in Caenorhabditis elegans DOI Creative Commons
Bharat Vivan Thapa, Mohit Das, James P Held

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Aminoacyl-tRNA synthetases (aaRSs) are essential for translation, as they charge tRNA molecules with their corresponding amino acids. Alterations in aaRSs can significantly disrupt both cytosolic and mitochondrial translation. Through a forward genetic screen unfolded protein response (UPR mt ) activators C. elegans , we identified missense mutation (P447V) the previously uncharacterized gene Y105E8A.20, which encodes dually localized methionine synthetase (MetRS). Here, characterize UPR induction by call mars-2 demonstrate that P447V allele is loss-of-function mutation. Furthermore, show impaired activity mitochondria triggers . This strain provides valuable tool studying translation understanding how involved homeostasis.

Язык: Английский

Процитировано

0