{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough the provided abstracts do not directly mention SYNJ2‐IT1, they offer a broad view of mitochondrial proteostasis and quality control mediated by the CLPP/CLPX system. These studies describe how loss or dysregulation of these proteases disrupts mitochondrial protein turnover, leading to deficits in proteostasis that manifest in diverse pathologies such as infertility, hearing loss, growth retardation, and metabolic imbalance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThey further detail that disturbances in mitochondrial proteolysis affect not only overall protein homeostasis but also specialized processes such as heme biosynthesis and energy supply during developmental transitions. In particular, alterations in the processing and turnover of key enzymes impact the mitochondrial unfolded protein response and even cellular signaling pathways (for example, mTORC1 over‐activation in gametogenesis), thereby underscoring the central role of the CLPXP complex in maintaining cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional investigations presented in these abstracts identify new substrates and interacting partners of the CLPP/CLPX machinery, linking mitochondrial protein quality control to nucleic acid-associated assemblies, metabolic enzyme complexes, and the regulation of stress responses. Although SYNJ2‐IT1 is not explicitly characterized in these reports, the mechanistic insights into the orchestration of enzyme condensates, retrograde signaling, and adaptive proteolysis provide a conceptual framework that might be relevant for understanding the potential regulatory roles of noncoding transcripts like SYNJ2‐IT1 in mitochondrial function. In light of these findings, future studies are warranted to determine whether SYNJ2‐IT1 modulates or interfaces with the CLPXP-driven proteostasis network, possibly influencing mitochondrial stress responses or enzymatic quality control."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Suzana Gispert, Dajana Parganlija, Michael Klinkenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of mitochondrial peptidase Clpp leads to infertility, hearing loss plus growth retardation via accumulation of CLPX, mtDNA and inflammatory factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt338"}], "href": "https://doi.org/10.1093/hmg/ddt338"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23851121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23851121"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Natalie Al-Furoukh, Alessandro Ianni, Hendrik Nolte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2015.06.016"}], "href": "https://doi.org/10.1016/j.bbamcr.2015.06.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26142927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26142927"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Eduard Hofsetz, Fatih Demir, Karolina Szczepanowska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Mouse Heart Mitochondria N Terminome Provides Insights into ClpXP-Mediated Proteolysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.RA120.002082"}], "href": "https://doi.org/10.1074/mcp.RA120.002082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32467259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32467259"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Catherine M Rondelli, Mark Perfetto, Aidan Danoff, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitous mitochondrial protein unfoldase CLPX regulates erythroid heme synthesis by control of iron utilization and heme synthesis enzyme activation and turnover."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2021.100972"}], "href": "https://doi.org/10.1016/j.jbc.2021.100972"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34280433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34280433"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jana Key, Sylvia Torres-Odio, Nina C Bach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells10123354"}], "href": "https://doi.org/10.3390/cells10123354"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34943861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34943861"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chenxi Guo, Yuan Xiao, Jingkai Gu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ClpP/ClpX deficiency impairs mitochondrial functions and mTORC1 signaling during spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Commun Biol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42003-023-05372-2"}], "href": "https://doi.org/10.1038/s42003-023-05372-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37798322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37798322"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jana Key, Suzana Gispert, Arvind Reddy Kandi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CLPP-Null Eukaryotes with Excess Heme Biosynthesis Show Reduced L-arginine Levels, Probably via CLPX-Mediated OAT Activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom14020241"}], "href": "https://doi.org/10.3390/biom14020241"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38397478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38397478"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jana Key, Suzana Gispert, Georg Auburger "}, {"type": "b", "children": [{"type": "t", "text": "Knockout Mouse Studies Show That Mitochondrial CLPP Peptidase and CLPX Unfoldase Act in Matrix Condensates near IMM, as Fast Stress Response in Protein Assemblies for Transcript Processing, Translation, and Heme Production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes15060694"}], "href": "https://doi.org/10.3390/genes15060694"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38927630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38927630"}]}]}]}