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ARMC1 shuttling regulates cellular mitochondrial distribution - Membrane Fractions

ABSTRACT: Mitochondria are platforms for important processes including mitochondrial fusion and fission, protein and lipid transport, cytoskeletal trafficking, and the activation of mitophagy, apoptosis, and innate immune responses. How cells regulate the assembly of protein complexes at the mitochondrial surface to control these dynamic functions is incompletely understood. Here, we show that ARMC1 shuttles between the cytosol and distinct mitochondrial complexes. The assembly of ARMC1 with Miro, MTFR, and TMEM11 links together mitochondrial trafficking and shaping activities and is essential for MTFR stability. In another complex, ARMC1 engages, via MTCH2, DNAJC11, which facilitates ARMC1 recycling back into the cytosol. Disrupting the balance of ARMC1 between these complexes leads to aberrant cellular mitochondrial distributions. Thus, the stability and function of the Miro-MTFR complex is regulated by ARMC1, whose mito-cytoplasmic shuttling via DNAJC11 tunes mitochondrial dynamics. Our findings provide a paradigm for protein complex regulation through the spatial control of a linchpin subunit.

INSTRUMENT(S): Orbitrap Eclipse, Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Felix Kraus

LAB HEAD: Dr Sichen Shao

PROVIDER: PXD054144 | Pride | 2025-03-19

REPOSITORIES: Pride

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Project description:A shotgun metagenome microarray was created and used to investigate gene transcription during vinyl chloride (VC) dechlorination by a microbial enrichment culture called KB1. The array was constructed by spotting genomic fragments amplified from short-insert libraries of KB1 metagenomic DNA. Subsequently, the microarrays were interrogated with RNA extracted from KB1 during VC dechlorination (VC+methanol), and in the absence of VC (methanol-only). The most differentially expressed spots, and spots with the highest intensities, were then chosen to be sequenced. Sequencing revealed that Dehalococcoides (Dhc) genes involved in transcription, translation and energy generation were up-regulated during VC degradation. Furthermore, the results indicated that the reductive dehalogenase homologous (RDH) gene KB1rdhA14 is the only RDH gene up-regulated upon VC degradation, and that multiple RDH genes were more highly transcribed in the absence of VC. Numerous hypothetical genes from Dehalococcoides were also more highly transcribed in methanol only treatments and indicate that many uncharacterized proteins are involved in cell maintenance in the absence of chlorinated substrates. Spots with genes from Spirochaetes, Chloroflexi, Geobacter, Methanogens and phage organisms were differentially expressed and sequencing provided information from these uncultivated organisms that can be used to design primers for more targeted studies. This array format is powerful, as it does not require a priori sequence knowledge. This study provides the first report of such arrays being used to investigate transcription in a mixed community, and shows that this array format can be used to screen metagenomic libraries for functionally important genes. 2 Biological replicate experimens conducted 1 month apart. In the first there were 2 dye-swapped duplicates (total 4) of VC+MeOH versus MeOH only. In the second experiment there was one set of dye swapped arrays. Thus 6 arrays were performed including biological replicates, dye swapped replicates and technical duplicates.

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ARMC1 shuttling regulates cellular mitochondrial distribution - Membrane Fractions

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