Biology subjects

McArthur, K.

Publications and source records attributed to McArthur, K..

6 recordsLinked to original sources

bioRxiv2026

Proximity labelling of the BAK macropore uncovers a new role for SLC35A4-MP in mitochondrial dynamics

Mitochondrial permeabilization by the apoptotic executioners BAK and BAX represents a critical stage of mitochondrial apoptosis and facilitates the release of pro-inflammatory mitochondrial DNA via herniation of the inner mitochondrial membrane. This study utilises TurboID proximity labelling to investigate the temporal changes of the BAK proximal proteome during mitochondrial herniation and apoptosis. In doing so, we detail a comprehensive BAK proximal proteome, both at steady state and during apoptosis and observe the loss of MICOS complex stability and proximity to the BAK pore as apoptosis proceeds. In addition, we identify the mitochondrial microprotein SLC35A4-MP proximal to the BAK pore and reveal a SLC35A4-MP dependent modulation of OPA1 processing. Furthermore, loss of SLC35A4-MP delays mitochondrial fragmentation in response to a variety of stressors, uncovering a previously unrecognised role for SLC35A4-MP in fine-tuning mitochondrial rearrangement during apoptotic stress.

cell biology↗

bioRxiv2026

Characterization of human Metaxin proteins reveals functional diversification of SAM37 homologs MTX1 and MTX3

The biogenesis of outer mitochondrial membrane {beta}-barrel proteins relies on the mitochondrial Sorting and Assembly Machinery (SAM) complex. In humans, the SAM complex contains SAM50 along with Metaxin (MTX) accessory subunits. MTX1 and MTX3 are homologous yet their functional similarities and differences have scarcely been investigated. Homozygous null mutations in the MTX2 gene are linked to a rare progeroid syndrome that causes severe depletion of MTX1. Here, we uncover unique phenotypes associated with the loss of MTX1 or MTX3 in human cells. Loss of MTX1 confers a deficiency in mitochondrial volume and causes network-wide mitochondrial morphology abnormalities. MTX3 loss resulted in negligible consequences for the biogenesis of {beta}-barrel proteins but resulted in increased mitochondrial mass. We also find that both MTX1 and MTX3 stability are dependent on the presence of MTX2, with MTX1 deficiency causing defective import and assembly. Collectively, our findings support the notion that MTX1 and MTX3 are functionally diverse homologs and are unlikely to be functionally redundant.

biochemistry↗

bioRxiv2025

From Archaea to the atmosphere: remotely sensing Arctic methane

Global atmospheric methane concentrations are rapidly rising and becoming isotopically more depleted, implying an unresolved microbial contribution. Rising Arctic temperatures are variably altering soil methane cycling, causing consequential uncertainty in the atmospheric methane budget. We demonstrated in an Arctic wetland that below-ground microbiota and methane-cycling features parallelled above-ground plant communities. To upscale emissions, we applied machine learning to remote sensing data to identify habitats, which were assigned average emissions. To upscale dynamically, we incorporated climate data, remotely-sensed water table variation, and habitat classes into a temporally-resolved biogeochemical model, to predict methane flux and isotope dynamics. This accurately estimated more depleted 13C-methane than previously used for Arctic habitats in global source partitioning. Remote-sensing of these rapidly changing inaccessible landscapes can thus help constrain the role of the Arctic in ongoing changes in global methane emissions.

microbiology↗

bioRxiv2025

In harmony? A scoping review of methods to combine multiple 16S amplicon data sets

Robust evidence on relationships between the human microbiome and health are critical for understanding and improving the human condition. However, there is little information about methodological approaches to combine and analyze multiple microbiome data sets. To address this gap, we conducted a scoping review of studies that combine sequencing data from multiple data sets to understand the study objectives, data sources and selection, feature -table assembly methods, and analyses. References were identified through a systematic search of literature published between 2011 and 2022. Our final review included 60 articles. Despite the wide-spread use of the word "meta-analysis," we found that only 24 studies used a systematic process to select their data sets, suggesting multiple meanings of the term within the field. While more than two thirds of studies used at least one publicly available data source, 19 had to request data from the original authors. Most studies (60%) combined data sets from multiple disjoint hypervariable regions. The number of hypervariable regions combined was not associated with the table construction method, but feature table construction method and the number of hypervariable regions influenced analytical resolution. Our results suggest the microbiome community needs to examine the use of terminology and analytic approaches for combining data sets; that additional work is needed to explore the impact of data source on bias in combined studies; and invite an independent evaluation of the methods used for feature table construction across disjoint regions.

microbiology↗

bioRxiv2023

Relative importance of MCL-1's Anti-Apoptotic versus Non-Apoptotic Functions in vivo

MCL-1 is an anti-apoptotic member of the BCL-2 protein family that ensures cell survival by blocking the intrinsic apoptotic cell death pathway1. MCL-1 is unique in being essential for early embryonic development and the survival of many cell types, including many cancer cells, which are not affected by the loss of the other anti-apoptotic BCL-2 family members1-4. Non-apoptotic functions of MCL-1 controlling mitochondrial ATP production and dynamics have been proposed to underlie this unique requirement for MCL-15-9. The relative contributions of the anti-apoptotic versus the non-apoptotic functions of MCL-1 in normal physiology have not been addressed. Here we replaced the coding sequence for MCL-1 with those for the anti-apoptotic proteins BCL-XL, BCL-2 or A1. We hypothesised that BCL-XL, BCL-2 and A1 may substitute for MCL-1 in the inhibition of apoptosis, but that they will not be able to replace MCL-1s non-apoptotic function. Strikingly, Mcl-1Bcl-xL/Bcl-xL and Mcl-1Bcl-2/Bcl-2 embryos survived to embryonic day 14.5, greatly surpassing the pre-implantation lethality of Mcl-1-/- embryos at E3.5. This demonstrates that the non-apoptotic functions of MCL-1 are dispensable for early development. However, at later stages of development and life after birth many cell types, particularly ones with high energy demand, were found to require both the anti-apoptotic and the non-apoptotic functions of MCL-1. These findings reveal the relative importance of these distinct functions of MCL-1 in physiology, providing important information for basic biology and the advancement of MCL-1 inhibitors in cancer therapy.

cell biology↗

bioRxiv2020

Epigenetic reprogramming of plasmacytoid dendritic cells drives type I interferon-dependent differentiation of acute myeloid leukemias for therapeutic benefit

Pharmacological inhibition of epigenetic enzymes can have therapeutic benefit, particularly against hematological malignancies. While these agents can affect tumor cell growth and proliferation, recent studies have demonstrated that pharmacological de-regulation of epigenetic modifiers may additionally mediate anti-tumor immune responses. Here we discovered a novel mechanism of immune regulation through the inhibition of histone deacetylases (HDACs). In a genetically engineered model of t(8;21) AML, leukemia cell differentiation and therapeutic benefit mediated by the HDAC inhibitor panobinostat required activation of the type I interferon (IFN) signaling pathway. Plasmacytoid dendritic cells (pDCs) were identified as the cells producing type I IFN in response to panobinostat, through transcriptional activation of IFN genes concomitant with increased H3K27 acetylation at these loci. Depletion of pDCs abrogated panobinostat-mediated activation of type I IFN signaling in leukemia cells and impaired therapeutic efficacy, while combined treatment of panobinostat and recombinant IFN improved therapeutic outcomes. These discoveries offer a new therapeutic approach for t(8;21) AML and demonstrate that epigenetic rewiring of pDCs enhances anti-tumor immunity, opening the possibility of exploiting this cell type as a new target for immunotherapy.

cancer biology↗