Transcript landscape in the heart of inducible cardiomyocyte-specific Immt knockout mice at 10 weeks after tamoxifen injection
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE322575 | GEO | 2026/04/01
REPOSITORIES: GEO
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Project description:Immt gene encodes Mic60 protein which is a main component of the mitochondrial contact site and cristae organizing system (MICOS) protein complex. The MICOS complex plays pivotal roles for crisa juction formation and connection of inner mitochondrial membrane and outer mitocondrial membrane of mitochondria. Although it is well known that the ristae are crucial for energy production by OXPHOS, it is still precisely unknown how the Mic60 is important in the adult matured cardiomyocytes in vivo. To expand our knowledge about the Mic60 functions in the adult mouse heart, we utilized inducible cardiomyocyte-specific Immt gene knockout mice and conducted bulk RNA-seq with the hearts. Our data highlights the mitochondria stress response at transcript level in the hearts.
2026-04-01 | GSE312894 | GEO
Project description:Virus-infected cells often exhibit dramatic cellular changes accompanied by altered mitochondrial function. The contribution of factors shaping the inner mitochondrial membrane (IMM) and cristae architecture on viral replication is insufficiently understood. Single cell transcriptomics applying vesicular stomatitis virus (VSV) infection suggests involvement of factors determining IMM architecture following infection. Consistently, inhibition of the F1Fo ATP synthase reduces viral replication which is associated with oligomerization of the complex and altered IMM structure. Moreover, deletion of mitochondrial contact site and cristae organizing system (MICOS) complex by targeting MIC60 results in reduced viral replication. Generation of Mic60inv/inv CD11c-Cre+ mice uncovers reduced crista junctions and viral replication in bone marrow-derived dendritic cells. Consequently, reduced viral replication in CD11c-expressing cells limits prolonged immune activation. Altogether, by linking the F1Fo ATP synthase and the MICOS complex to viral replication and immune activation, we describe links between the mitochondrial structure-metabolism and the immune response against viral infection.
2025-05-14 | GSE297187 | GEO
Project description:Molecules that contribute to membrane curvature are essential for the formation of cristae, the bioenergetic subcompartments of mitochondria. Mic60 may be the oldest of these factors as its prokaryotic ortholog is also needed for bioenergetic-subcompartment formation in extant alphaproteobacteria, the closest organismal relatives to mitochondria. In prokaryotes and eukaryotes, Mic60 exhibits an invariable structure: the characteristic C-terminal mitofilin domain, a central coiled coil, and N-proximal transmembrane domain. Moreover, mitochondrial Mic60 is a central subunit of virtually all iterations of the crista-shaping MICOS multiprotein complex. Yet, no mic60 is detected in any genomes of Euglenozoa, an expansive phylum containing trypanosomes. Here, we show that Mic60 has been replaced in euglenazoans by two cryptic mitofilin-containing MICOS subunits, Mic34 and Mic40. Sharply contrasting Mic60 from two domains of life, these are not integral membrane proteins. Reverse genetics revealed they are intertwined with the oxidative folding protein import pathway required for mitochondrial–and crista–biogenesis, likely masking a potential membrane remodeling role. Nevertheless, Mic34 binds to phospholipid bilayers in vitro. Mic34 and Mic40 heterologous expression remodels gammaproteobacterial cytoplasmic membranes, like prokaryotic and eukaryotic Mic60. Astoundingly, Mic34 overexpression transiently elaborates the simplified tubular mitochondrion of a life cycle stage of Trypanosoma brucei with repressed oxidative phosphorylation. Using Mic34’s mitofilin structural homology to Mic60’s, we predicted mutations to a conserved mitofilin motif that ablated Mic34’s mitochondria-remodeling activity. Thus, we have expanded the mitofilin family of proteins to encompass diverged proteins that unconventionally implement mitofilin in nature.
2025-12-01 | PXD059459 | Pride
Project description:Mitochondrial cristae are polymorphic invaginations of the inner membrane that are the fabric of cellular respiration. Both the Mitochondrial Contact Site and Cristae Organization System (MICOS) and the F1FO-ATP synthase are vital for sculpting cristae by opposing membrane bending forces. While MICOS promotes negative curvature at cristae junctions, dimeric F1FO-ATP synthase is crucial for positive curvature at cristae rims. Crosstalk between these two complexes has been observed in baker’s yeast, the model organism of the Opisthokonta supergroup. Here, we report that this property is conserved in Trypanosoma brucei, a member of the Discoba supergroup that separated from Opisthokonta ~2 billion years ago. Specifically, one of the paralogs of the core MICOS subunit Mic10 interacts with dimeric F1FO-ATP synthase, whereas the other core Mic60 subunit has a counteractive effect on F1FO-ATP synthase oligomerization. This is evocative of the nature of MICOS-F1FO-ATP synthase crosstalk in yeast, which is remarkable given the diversification these two complexes have undergone during almost 2 eons of independent evolution. Furthermore, we identified a highly diverged trypanosome homolog of subunit e, which is essential for the stability of F1FO-ATP synthase dimers in yeast. Just like subunit e, it is preferentially associated with dimers, interacts with Mic10 and its silencing results in severe defects to cristae and disintegration of F1FO-ATP synthase dimers. Our findings indicate that crosstalk between MICOS and dimeric F1FO-ATP synthase is a fundamental property impacting cristae shape throughout eukaryotes.
2021-06-15 | PXD025109 | Pride
Project description:Virus-infected cells often exhibit dramatic cellular changes accompanied by altered mitochondrial function. The contribution of factors shaping the inner mitochondrial membrane (IMM) and cristae architecture on viral replication is insufficiently understood. Single cell transcriptomics applying vesicular stomatitis virus (VSV) infection suggests involvement of factors determining IMM architecture following infection. Consistently, inhibition of the F1Fo ATP synthase reduces viral replication which is associated with oligomerization of the complex and altered IMM structure. Moreover, deletion of mitochondrial contact site and cristae organizing system (MICOS) complex by targeting MIC60 results in reduced viral replication. Generation of Mic60inv/inv CD11c-Cre+ mice uncovers reduced crista junctions and viral replication in bone marrow-derived dendritic cells. Consequently, reduced viral replication in CD11c-expressing cells limits prolonged immune activation. Altogether, by linking the F1Fo ATP synthase and the MICOS complex to viral replication and immune activation, we describe links between the mitochondrial structure-metabolism and the immune response against viral infection.
2025-06-24 | MTBLS12437 | MetaboLights
Project description:Virus-infected cells often exhibit dramatic cellular changes accompanied by altered mitochondrial function. The contribution of factors shaping the inner mitochondrial membrane (IMM) and cristae architecture on viral replication is insufficiently understood. Single cell transcriptomics applying vesicular stomatitis virus (VSV) infection suggests involvement of factors determining IMM architecture following infection. Consistently, inhibition of the F1Fo ATP synthase reduces viral replication which is associated with oligomerization of the complex and altered IMM structure. Moreover, deletion of mitochondrial contact site and cristae organizing system (MICOS) complex by targeting MIC60 results in reduced viral replication. Generation of Mic60inv/inv CD11c-Cre+ mice uncovers reduced crista junctions and viral replication in bone marrow-derived dendritic cells. Consequently, reduced viral replication in CD11c-expressing cells limits prolonged immune activation. Altogether, by linking the F1Fo ATP synthase and the MICOS complex to viral replication and immune activation, we describe links between the mitochondrial structure-metabolism and the immune response against viral infection.
2025-06-18 | MTBLS12438 | MetaboLights
Project description:Mitochondrial damage causes mtDNA release to activate type I interferon (IFN-I) response via the cGAS-STING pathway. mtDNA-induced inflammation promotes autoimmune and aging-related degenerative disorders. However, the global picture of inflammation-inducing mitochondrial damages remains obscure. Here we performed a mitochondria-targeted CRISPR-knockout screen for regulators of the IFN-I response. Strikingly, our screen revealed dozens of hits enriched with key regulators of cristae architecture, including phospholipid cardiolipin and protein complexes such as OPA1, MICOS, SAM, MIB, PHB, and the F1Fo-ATP synthase. Disrupting these cristae organizers consistently induced mtDNA release and STING-dependent IFN-I response. Furthermore, robust STING-dependent IFN-I response was induced in vivo by knocking out MTX2, a subunit of the SAM complex whose null-mutations cause progeria in human. Taken together, beyond revealing the central role of cristae architecture to prevent mtDNA release and inflammation, our results mechanistically link mitochondrial cristae disorganization and inflammation, two emerging hallmarks of aging and aging-related degenerative diseases.
2022-10-28 | GSE216499 | GEO
Project description:Mitochondrial cytochrome c oxidase, the complex IV of the respiratory chain, is assembled in a modular fashion from mitochondrial- as well as nuclear-encoded subunits, guided by numerous assembly factors. This intricate process is further complicated by the characteristic architecture of the inner mitochondrial membrane with its functional asymmetry. The mitochondrial contact site and cristae organizing system (MICOS) maintains the stability of crista junctions that connect the cristae, the site of mitochondrial respiration, with the inner boundary membrane where newly imported respiratory subunits first arrive. Here, we report that MICOS facilitates specific assembly steps of complex IV and associates with intermediates of the Cox1 and Cox3 modules. Moreover, MICOS recruits a variety of assembly factors even in the absence of ongoing complex IV biogenesis. Our results establish MICOS as an important agent in efficient respiratory chain assembly that directly supports and coordinates complex IV biogenesis within the complex inner membrane architecture.
2025-12-11 | PXD069632 | JPOST Repository
Project description:Mitochondria are the metabolic center and powerhouses of cells by coordinating the tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) and electron transport to generate ATP, which provide energy for cell survival and functional maintenance. This is attributed to the key structure of mitochondria cristae, which are formed by the inward folding of inner mitochondrial membranes. Numerous studies have demonstrated that RNA-binding proteins play an important role in maintaining the normal structure and function of mitochondria. However, the relevant mechanism remains unclear. Here, we report that the RNA-binding protein LARP-1 affects the structure and function of mitochondria by disrupting crista-related proteins, including the MICOS complex, respiratory chain complexes, and the proton-transporting ATP synthase complex. Using APEX-based proximity labeling assays, we pulled down mRNAs associated with LARP-1::APEX2, and determined the identities of mRNAs by sequencing. Among the 653 LARP-1::APEX2-enriched mRNAs, 37.5% (245/653) encode mitochondrial proteins, of which 71.8% (176/245) were identified to be down-regulated in larp-1 mutants by LC-MS analysis of purified mitochondria. In addition, mRNAs encoding components of the MICOS complex, respiratory chain complexes, and ATP synthase complex were strongly enriched, suggesting that they were associated with LARP-1.
2025-06-22 | GSE300049 | GEO
Project description:Regulator of chromosome condensation domain-containing protein 1 (RCCD1) plays an important role in chromosome segregation and microtubule stability in the nucleus and has been identified recently as a potential driver for breast cancer. We report here that, unexpectedly, RCCD1 is also localized in mitochondria. We show that RCCD1 resides in the mitochondrial inner membrane, where it interacts with the mitochondrial contact site/cristae organizing system (MICOS) and mitochondrial DNA (mtDNA) to regulate mitochondrial nucleoid organization, thereby influencing mtDNA transcription, oxidative phosphorylation, and the production of reactive oxygen species. Interestingly, RCCD1 is upregulated under hypoxic conditions, leading to decreased generation of reactive oxygen species and alleviated apoptosis favoring cancer cell survival. We show that RCCD1 promotes breast cancer cell proliferation in vitro and accelerates breast tumor growth in vivo. Indeed, RCCD1 is overexpressed in breast carcinomas, and its level of expression is associated with aggressive breast cancer phenotypes and poor patient survival. Our study reveals an additional dimension in RCCD1 functionality, indicating RCCD1 is an essential regulator of mtDNA dynamics and mitochondrial homeostasis, whose dysregulation inflicts pathologic states such as breast cancer.
2023-12-01 | GSE219134 | GEO