Ask about this productRelated genes to: HMOX2 protein
- Gene:
- HMOX2 NIH gene
- Name:
- heme oxygenase 2
- Previous symbol:
- -
- Synonyms:
- HO-2
- Chromosome:
- 16p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1992-10-15
- Date modifiied:
- 2017-12-15
Related products to: HMOX2 protein
Related articles to: HMOX2 protein
- Intracellular organelles do not function in isolation but instead cooperate through organelle contact sites, where membranes closely appose without fusion to exchange information and metabolites. Among these interfaces, mitochondria-endoplasmic reticulum contact sites (MERCs) have emerged as central regulatory hubs involved not only in calcium and lipid exchange but also in mitochondrial dynamics, autophagy, stress responses, cell death, and metabolic regulation. In this review, the molecular basis of MERC formation is first organized from the perspectives of tethering, molecular transfer, and contact-site regulation, emphasizing that MERCs represent dynamic functional domains that are reorganized according to cellular conditions rather than static structures. Our recent findings are then introduced demonstrating that the mitochondrial outer membrane E3 ubiquitin ligase MITOL (also known as MARCHF5) selectively modulates substrate activity at MERCs and may contribute to mitochondrial iron supply and respiratory maintenance through regulation of the heme-degrading enzyme HMOX2. Because MERCs undergo rapid and reversible remodeling, quantitative analysis in living cells is essential. A split-luciferase-based reversible assay is presented as an example of an approach for real-time monitoring of MERC dynamics, revealing a stress-responsive increase in MERCs triggered by mitochondrial reactive oxygen species that is linked to the handling of lipid radicals. Finally, current methodologies for MERC analysis, including electron microscopy, super-resolution imaging, proximity sensors, and proximity labeling, are overviewed. - Source: PubMed
Shiiba Isshin - Dilated cardiomyopathy (DCM) is the most common non-ischemic cardiomyopathy and a major cause of heart failure, but disease-specific molecular biomarkers remain limited. This study aimed to identify and prioritize tissue-level, disease-responsive candidate biomarkers for DCM using an integrative multi-omics bioinformatics framework. - Source: PubMed
Publication date: 2026/06/09
Li JingweiSong ZhongyangWang GuanweiChen YuchanCheng JiamiaoZhang Zhiming - Children with juvenile idiopathic arthritis (JIA) are reported to exhibit increased rates of symptoms affecting emotional regulation and behaviour. However, underlying biological mechanisms remain unclear. Inflammation in the central nervous system (CNS) can be triggered by peripheral immune effects and may contribute to these observations. In this study, we aimed to investigate whether neurobiological alterations are present in systemic JIA (sJIA), whether CNS inflammation occurs during arthritis, and the potential underlying mechanisms. - Source: PubMed
Publication date: 2026/06/16
Wen XingzhaoQu HeshuangBenedyk-Machaczka MalgorzataChen DaphneSundberg ErikMelén ErikAltman MariaAulin CeciliaHarris Helena Erlandsson - Mitochondrial iron dynamics are essential for cellular respiration and metabolic homeostasis, yet the molecular mechanisms governing iron supply to mitochondria remain poorly understood. Here we identify a pathway in which haem serves as an iron source for mitochondria, maintaining mitochondrial iron homeostasis and mitochondrial supercomplex integrity, regulated at mitochondria-endoplasmic reticulum contact sites (MERCs). We demonstrate that haem oxygenase 2 (HMOX2), an ER-resident enzyme, is also localized to MERCs and facilitates the supply of haem-derived iron to mitochondria. This process is orchestrated by the mitochondrial ubiquitin ligase MITOL (also known as MARCH5/MARCHF5), which ubiquitinates HMOX2 at K68 with K63-linked polyubiquitin chains, enhancing its haem-degrading activity. Notably, loss of HMOX2 or disruption of MITOL-mediated ubiquitination impairs mitochondrial iron homeostasis and mitochondrial respiration. These findings establish a paradigm in which MERCs function as an iron supply hub, integrating haem metabolism with mitochondrial iron utilization. - Source: PubMed
Publication date: 2026/06/10
Oshio HijiriShiiba IsshinIto NaokiOkada NaozumiYamaguchi FuyaIshikawa YutoNagashima ShunFujikawa YuutaUmezawa KeitaroMiura YuriShimizu MisakiSaito YoshiroYamaguchi TomoyukiInatome RyokoYanagi Shigeru - Interstitial lung disease (ILD) is an important adverse event related to deruxtecan-based antibody-drug conjugates (DXd ADCs). Understanding mechanisms and translationally relevant preclinical models remain incompletely defined. Here, we established a reproducible cynomolgus monkey model of DXd ADC-related ILD and performed the first integration of bronchoalveolar lavage fluid (BALF) extracellular vesicle (EV) proteomics with lung single-cell RNA sequencing (scRNA-seq). Weekly intravenous administration of a target-nonbinding human IgG1 DXd ADC to cynomolgus monkeys for 12 weeks consistently induced interstitial pneumonitis in all animals, with radiologic abnormalities emerging by Week 6 and progressing thereafter. Longitudinal SomaScan-based proteomic analyses revealed a pronounced and selective increase in differentially expressed proteins (DEPs) in BALF-derived EVs from Week 6 onward, exceeding changes observed in plasma or bulk BALF. Gene Ontology analysis showed enrichment of inflammatory, wound repair/regeneration, and extracellular matrix remodeling pathways within the BALF EV compartment. Integration of BALF EV proteomics with lung scRNA-seq demonstrated strong concordance between EV-associated signatures and transcriptional programs in alveolar epithelial, mesenchymal, and immune cell populations. Core injury-associated genes, including FN1, TIMP1, and COL3A1, were broadly upregulated across cell types, along with cell-type-restricted signatures including AT1 cells (BMP4, HMOX2), AT2 cells (CXCL2, SIRPA), fibroblasts (TNC, IGF1), endothelial cells (LCP1, CXCL12), neutrophils (ADAM17), and macrophages (CD84, HAVCR2, CXCL10). Together, this study defines a robust cynomolgus monkey model of DXd ADC-related ILD and identifies BALF EVs as a sensitive, lung-localized molecular readout and a promising translational source of mechanistic insights. - Source: PubMed
Publication date: 2026/05/25
Kumagai KazuyoshiIguchi TakumaKubota KentaroSakurai KenTsuchiya YoshimiChiba Katsuyoshi