Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RGS12 is required for the maintenance of mitochondrial function during skeletal development.

ABSTRACT: Mitochondrial morphology and function are crucial for tissue homeostasis, such as for skeletal development, but the cellular and molecular mechanisms remain unclear. Here, we provide evidence that regulator of G-protein signaling 12 (RGS12) is present in the mitochondria of primary chondrocytes and cartilage tissues. Deletion of RGS12 in type II collagen-positive cells led to a significant decrease in mitochondrial number, membrane potential, and oxidative phosphorylation function. Mechanistically, RGS12 promoted the function of ATP5A as an enhancer of tyrosine phosphorylation. Mice with RGS12 deficiency in the chondrocyte lineage showed serious body retardation, decreased bone mass, and chondrocyte apoptosis due to the defective activity of ATP synthase. To our knowledge, this is the first report that RGS12 is required for maintaining the function of mitochondria, which may allow it to orchestrate responses to cellular homeostasis.

SUBMITTER: Yuan G

PROVIDER: S-EPMC7459111 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

RGS12 is required for the maintenance of mitochondrial function during skeletal development.

Yuan Gongsheng G Yang Shuting S Liu Min M Yang Shuying S

Cell discovery 20200901

Mitochondrial morphology and function are crucial for tissue homeostasis, such as for skeletal development, but the cellular and molecular mechanisms remain unclear. Here, we provide evidence that regulator of G-protein signaling 12 (RGS12) is present in the mitochondria of primary chondrocytes and cartilage tissues. Deletion of RGS12 in type II collagen-positive cells led to a significant decrease in mitochondrial number, membrane potential, and oxidative phosphorylation function. Mechanistical ...[more]

PMID: 32922858

Similar Datasets

CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.

Project description:Mitochondria play a central role in muscle metabolism and function. A unique family of iron-sulfur proteins, termed CDGSH Iron Sulfur Domain-containing (CISD/NEET) proteins, support mitochondrial function in skeletal muscles. The abundance of these proteins declines during aging leading to muscle degeneration. Although the function of the outer mitochondrial CISD/NEET proteins, CISD1/mitoNEET and CISD2/NAF-1, has been defined in skeletal muscle cells, the role of the inner mitochondrial CISD protein, CISD3/MiNT, is currently unknown. Here, we show that CISD3 deficiency in mice results in muscle atrophy that shares proteomic features with Duchenne muscular dystrophy. We further reveal that CISD3 deficiency impairs the function and structure of skeletal muscles, as well as their mitochondria, and that CISD3 interacts with, and donates its [2Fe-2S] clusters to, complex I respiratory chain subunit NADH Ubiquinone Oxidoreductase Core Subunit V2 (NDUFV2). Using coevolutionary and structural computational tools, we model a CISD3-NDUFV2 complex with proximal coevolving residue interactions conducive of [2Fe-2S] cluster transfer reactions, placing the clusters of the two proteins 10 to 16 Å apart. Taken together, our findings reveal that CISD3/MiNT is important for supporting the biogenesis and function of complex I, essential for muscle maintenance and function. Interventions that target CISD3 could therefore impact different muscle degeneration syndromes, aging, and related conditions.

| S-EPMC11145280 | biostudies-literature

CISD3 is required for Complex I function, mitochondrial integrity, and skeletal muscle maintenance

Project description:Mitochondria play a central role in muscle metabolism and function. In skeletal muscles, a unique family of iron-sulfur proteins, termed CISD proteins, support mitochondrial function. The level of these proteins declines with age leading to muscle degeneration. Although the function of the outer mitochondrial proteins CISD1 and CISD2 was defined, the role of the inner mitochondrial protein CISD3, is currently unknown. Here we show that CISD3 deficiency in mice results in muscle atrophy that shares proteomic features with Duchenne Muscular Dystrophy. We further reveal that CISD3 deficiency impairs the function and structure of skeletal muscle mitochondria, and that CISD3 interacts with, and donates its clusters to, Complex I respiratory chain subunit NDUFV2. These findings reveal that CISD3 is important for supporting the biogenesis and function of Complex I, essential for muscle maintenance and function. Interventions that target CISD3 could therefore impact muscle degeneration syndromes, aging, and related conditions.

2024-05-07 | PXD042593 | Pride

PARP12 is required for mitochondrial function maintenance in thermogenic adipocytes.

Project description:PARP12 is a member of poly-ADP-ribosyl polymerase (PARPs), which has been characterized for its antiviral function. Yet its physiological implication in adipocytes remains unknown. Here, we report a central function of PARP12 in thermogenic adipocytes. We show that PARP12 is highly expressed in brown adipose tissue and is mainly localized to the mitochondria. Knockdown of PARP12 in vitro reduced UCP1 expression. In parallel, the deficiency of PARP12 reduced mitochondrial respiration in adipocytes, while overexpression of PARP12 reversed these effects.

| S-EPMC9351573 | biostudies-literature

LncRNA NEAT1 controls the lineage fates of BMSCs during skeletal aging by impairing mitochondrial function and pluripotency maintenance.

Project description:Aged bone marrow mesenchymal stem cells (BMSCs) exhibit aberrant self-renewal and lineage specification, which contribute to imbalanced bone-fat and progressive bone loss. In addition to known master regulators of lineage commitment, it is crucial to identify pivotal switches governing the specific differentiation fate of aged BMSCs. Here, we profiled differences in epigenetic regulation between adipogenesis and osteogenesis and identified super-enhancer associated lncRNA nuclear-enriched abundant transcript 1 (NEAT1) as a key bone-fat switch in aged BMSCs. We validated that NEAT1 with high enhancer activity was transcriptionally activated by ATF2 and directed aged BMSCs to a greater propensity to differentiate toward adipocytes than osteoblasts by mediating mitochondrial function. Furthermore, we confirmed NEAT1 as a protein-binding scaffold in which phosphorylation modification of SOX2 Ser249/250 by CDK2 impaired SOX2/OCT4 complex stability and dysregulated downstream transcription networks of pluripotency maintenance. In addition, by sponging miR-27b-3p, NEAT1 upregulated BNIP3L, BMP2K, and PPARG expression to shape mitochondrial function and osteogenic/adipogenic differentiation commitment, respectively. In extracellular communication, NEAT1 promoted CSF1 secretion from aged BMSCs and then strengthened osteoclastic differentiation by extracellular vesicle delivery. Notably, Neat1 small interfering RNA delivery induced increased bone mass in aged mice and decreased fat accumulation in the bone marrow. These findings suggest that NEAT1 regulates the lineage fates of BMSCs by orchestrating mitochondrial function and pluripotency maintenance, and might be a potential therapeutic target for skeletal aging.

| S-EPMC8816946 | biostudies-literature

Mutant desmin substantially perturbs mitochondrial morphology, function and maintenance in skeletal muscle tissue.

Project description:Secondary mitochondrial dysfunction is a feature in a wide variety of human protein aggregate diseases caused by mutations in different proteins, both in the central nervous system and in striated muscle. The functional relationship between the expression of a mutated protein and mitochondrial dysfunction is largely unknown. In particular, the mechanism how this dysfunction drives the disease process is still elusive. To address this issue for protein aggregate myopathies, we performed a comprehensive, multi-level analysis of mitochondrial pathology in skeletal muscles of human patients with mutations in the intermediate filament protein desmin and in muscles of hetero- and homozygous knock-in mice carrying the R349P desmin mutation. We demonstrate that the expression of mutant desmin causes disruption of the extrasarcomeric desmin cytoskeleton and extensive mitochondrial abnormalities regarding subcellular distribution, number and shape. At the molecular level, we uncovered changes in the abundancy and assembly of the respiratory chain complexes and supercomplexes. In addition, we revealed a marked reduction of mtDNA- and nuclear DNA-encoded mitochondrial proteins in parallel with large-scale deletions in mtDNA and reduced mtDNA copy numbers. Hence, our data demonstrate that the expression of mutant desmin causes multi-level damage of mitochondria already in early stages of desminopathies.

| S-EPMC4992032 | biostudies-literature

Ccn6 Is Required for Mitochondrial Integrity and Skeletal Muscle Function in Zebrafish.

Project description:Mutations in the CCN6 (WISP3) gene are linked with a debilitating musculoskeletal disorder, termed progressive pseudorheumatoid dysplasia (PPRD). Yet, the functional significance of CCN6 in the musculoskeletal system remains unclear. Using zebrafish as a model organism, we demonstrated that zebrafish Ccn6 is present partly as a component of mitochondrial respiratory complexes in the skeletal muscle of zebrafish. Morpholino-mediated depletion of Ccn6 in the skeletal muscle leads to a significant reduction in mitochondrial respiratory complex assembly and activity, which correlates with loss of muscle mitochondrial abundance. These mitochondrial deficiencies are associated with notable architectural and functional anomalies in the zebrafish muscle. Taken together, our results indicate that Ccn6-mediated regulation of mitochondrial respiratory complex assembly/activity and mitochondrial integrity is important for the maintenance of skeletal muscle structure and function in zebrafish. Furthermore, this study suggests that defects related to mitochondrial respiratory complex assembly/activity and integrity could be an underlying cause of muscle weakness and a failed musculoskeletal system in PPRD.

| S-EPMC7905066 | biostudies-literature

Cavin4b/Murcb Is Required for Skeletal Muscle Development and Function in Zebrafish.

Project description:Skeletal muscles provide metazoans with the ability to feed, reproduce and avoid predators. In humans, a heterogeneous group of genetic diseases, termed muscular dystrophies (MD), lead to skeletal muscle dysfunction. Mutations in the gene encoding Caveolin-3, a principal component of the membrane micro-domains known as caveolae, cause defects in muscle maintenance and function; however it remains unclear how caveolae dysfunction underlies MD pathology. The Cavin family of caveolar proteins can form membrane remodeling oligomers and thus may also impact skeletal muscle function. Changes in the distribution and function of Cavin4/Murc, which is predominantly expressed in striated muscles, have been reported to alter caveolae structure through interaction with Caveolin-3. Here, we report the generation and phenotypic analysis of murcb mutant zebrafish, which display impaired swimming capacity, skeletal muscle fibrosis and T-tubule abnormalities during development. To understand the mechanistic importance of Murc loss of function, we assessed Caveolin-1 and 3 localization and found it to be abnormal. We further identified an in vivo function for Murc in Erk signaling. These data link Murc with developmental defects in T-tubule formation and progressive muscle dysfunction, thereby providing a new candidate for the etiology of muscular dystrophy.

| S-EPMC4905656 | biostudies-literature

Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis.

Project description:BackgroundTid1 is a mitochondrial co-chaperone protein and its transcript is abundantly expressed in skeletal muscle tissues. However, the physiological function of Tid1 during skeletal myogenesis remains unclear.MethodsIn vitro induced differentiation assay of mouse myoblast C2C12 cells was applied to examine the physiological role of Tid1 during skeletal myogenesis. In addition, transgenic mice with muscle specific (HSA-Cre) Tid1 deletion were established and examined to determine the physiological function of Tid1 during skeletal muscle development in vivo.ResultsExpression of Tid1 protein was upregulated in the differentiated C2C12 cells, and the HSA-Tid1f/f mice displayed muscular dystrophic phenotype. The expression of myosin heavy chain (MyHC), the protein served as the muscular development marker, was reduced in HSA-Tid1f/f mice at postnatal day (P)5 and P8. The protein levels of ATP sensor (p-AMPK) and mitochondrial biogenesis protein (PGC-1α) were also significantly reduced in HSA-Tid1f/f mice. Moreover, Tid1 deficiency induced apoptotic marker Caspase-3 in muscle tissues of HSA-Tid1f/f mice. Consistent with the in vivo finding, we observed that downregulation of Tid1 not only reduced the ATP production but also abolished the differentiation ability of C2C12 cells by impairing the mitochondrial activity.ConclusionTogether, our results suggest that Tid1 deficiency reduces ATP production and abolishes mitochondrial activity, resulting in energy imbalance and promoting apoptosis of muscle cells during myogenesis. It will be of importance to understand the function of Tid1 during human muscular dystrophy in the future.

| S-EPMC5143475 | biostudies-literature

Distinct function of P63 isoforms during embryonic skeletal development.

Project description:P63 belongs to the P53 family of transcription factors. There are multiple P63 isoforms that play important functions both in cancer and development. The obvious limb defect in p63 null mice and in human skeletal syndromes with P63 mutations suggest its essential role in long bone development. However, how the different P63 isoforms function during long bone development is largely unknown. We have previously shown that TAP63?, the longest P63 isoform, plays a positive role in embryonic skeletal development, since targeting TAP63? expression in hypertrophic chondrocytes accelerates endochondral ossification at both E17.5 and P1 stages. Here, we report transgenic studies of ?NP63?, another P63 isoform which lacks the N-terminal transactivation domain compared to TAP63?, using the same hypertrophic chondrocyte-specific Col10a1 control element. No skeletal abnormalities were detected in these Col10a1-?NP63? transgenic mice at both E17.5 and P1 stages, suggesting less importance of ?NP63? during late embryonic skeletal development. To further investigate the function of P63 isoforms during early skeletal development, we have generated ?NP63? and TAP63? transgenic mice using a chondrocyte-specific Col2a1 control element. Surprisingly, while no skeletal defect was shown in the Col2a1-?NP63? transgenic mice, reduced ossification was observed in the digit and tail bones of Col2a1-TAP63? transgenic mice at both E17.5 and P1 stages compared to their wild-type littermates. Expression profiling and immunohistochemical analysis detected upregulated expression of Sox9, a major negative regulator of endochondral ossification, in Col2a1-TAP63? transgenic mice. Taken together, our results suggest a distinct function of P63 isoforms, herein, ?NP63? and TAP63?, during endochondral ossification.

| S-EPMC3628837 | biostudies-literature

Fe(III) Is Essential for Porcine Embryonic Development via Mitochondrial Function Maintenance.

Project description:Iron is an important trace element involved in several biological processes. The role of iron in porcine early embryonic development remains unknown. In the present study, we depleted iron (III, Fe3+) with deferoxamine (DFM), a specific Fe3+ chelator, in cultured porcine parthenotes and monitored embryonic development, apoptosis, mitochondrial membrane potential, and ATP production. Results showed biphasic function of Fe3+ in porcine embryo development. 0.5 μM DFM obviously increased blastocyst formation (57.49 ± 2.18% vs. control, 43.99 ± 1.72%, P < 0.05) via reduced (P < 0.05) production of reactive oxygen species (ROS), further increased mitochondrial membrane potential and ATP production in blastocysts (P < 0.05). 0.5 μM DFM decreased mRNA expression of Caspase 3 (Casp3) and increased Bcl-xL. However, results showed a significant reduction in blastocyst formation in the presence of 5.0 μM DFM compared with the control group (DFM, 21.62 ± 3.92% vs. control, 43.99 ± 1.73%, P < 0.05). Fe3+ depletion reduced the total (DFM, 21.10 ± 8.78 vs. control, 44.09 ± 13.65, P < 0.05) and increased apoptotic cell number (DFM, 11.10 ± 5.24 vs. control, 2.64 ± 1.43, P < 0.05) in the blastocyst. An obvious reduction in mitochondrial membrane potential and ATP level after 5.0 μM DFM treatment was observed. Co-localization between mitochondria and cytochrome c was reduced after high concentration of DFM treatment. In conclusion, Fe3+ is essential for porcine embryonic development via mitochondrial function maintenance, but redundant Fe3+ impairs the function of mitochondria.

| S-EPMC4498905 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data