MGC4618 antibody - N-terminal region (ARP34360_T100)
- Known as:
- MGC4618 (anti-) - N-terminal region (ARP34360_T100)
- Catalog number:
- arp34360_t100
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- MGC4618 antibody - N-terminal region (ARP34360_T100)
Related genes to: MGC4618 antibody - N-terminal region (ARP34360_T100)
- Gene:
- TMEM175 NIH gene
- Name:
- transmembrane protein 175
- Previous symbol:
- -
- Synonyms:
- MGC4618
- Chromosome:
- 4p16.3
- Locus Type:
- gene with protein product
- Date approved:
- 2006-08-29
- Date modifiied:
- 2015-09-29
Related products to: MGC4618 antibody - N-terminal region (ARP34360_T100)
Related articles to: MGC4618 antibody - N-terminal region (ARP34360_T100)
- Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, in which lysosomal acidification and hydrolytic activity are crucial for effective pathogen clearance by macrophages. Transmembrane Protein 175 (TMEM175) is a key regulator of lysosomal pH, and its deficiency is reported to cause lysosomal over-acidification and impaired cathepsin D (CTSD) activity. However, the role of TMEM175 in sepsis remains uncertain. We hypothesize that TMEM175 deficiency exacerbates sepsis by impairing CTSD activity. TMEM175 mRNA expression levels were measured in peripheral blood mononuclear cells (PBMCs) from septic patients and healthy controls (HCs). Using a cecal ligation and puncture (CLP) mouse model, we evaluated the effects of the TMEM175 inhibitor 2-phenylcyclopentylamine (2-PPA) on mortality and bacterial load in target organs. In vitro, TMEM175-knockdown in macrophages was performed to assess its impact on bacterial clearance, phagocytosis, lysosomal acidification, and cathepsin maturation. Results showed that TMEM175 expression was significantly downregulated in PBMCs from septic patients. Pharmacological inhibition of TMEM175 in CLP mice exacerbated bacterial burden and increased mortality. Mechanistically, TMEM175 deficiency impaired macrophage-mediated bacterial clearance, despite having no effect on the initial phagocytic uptake. This dysfunction was attributed to TMEM175, which directly regulates cathepsin transcription. Additionally, TMEM175 deficiency suppressed PI3K-Akt signaling, reducing inflammatory cytokine production. - Source: PubMed
Bai ZhenzhenPeng BeiLuo TaoSun Lingbin - TMEM175 is the pore-forming subunit of a lysosomal K+ channel complex that regulates lysosomal pH stability and membrane potential. To further investigate its cellular functions and implications in neurodegenerative diseases, antibody reagents are needed. Here we have characterized six TMEM175 commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs. - Source: PubMed
Publication date: 2026/06/16
Moleón Vera RuízAlende CharlesFothouhi MaryamBolívar Sara GonzálezAyoubi RihamFrancis VincentMcPherson Peter SLaflamme Carl - Many age-related neurodegenerative disorders are marked by progressive defects in cellular energy metabolism and protein homeostasis that converge on mitochondrial and lysosomal dysfunction. TLDc domain-containing proteins, such as OXR1, NCOA7, and related family members, have emerged as crucial modulators of organellar physiology and cellular stress responses. Growing evidence indicates that TLDc proteins physically interact with vacuolar ATPases (V-ATPases) to modulate their assembly and catalytic activity, linking TLDc function directly to the maintenance of lysosomal and Golgi lumen pH. This organellar pH homeostasis, in turn, is fundamental to intracellular iron handling and metabolic regulation, processes essential for mitochondrial bioenergetics, lysosomal functions, and cellular viability. Lysosomes maintain an acidic lumen via V-ATPase proton pumping, counterbalanced by specific ion channels, including TMEM175. This acidic environment is required for ferric iron reduction and subsequent release into the cytosol; when acidification fails, cells develop cytosolic iron deficiency, mitochondrial defects, pseudohypoxia via HIF-1α activation, and inflammation. Conversely, iron flux from lysosomes to mitochondria depends on acidic conditions and direct organelle contact, as exemplified by BDH2-driven siderophore transport, a V-ATPase-dependent but not TLDc-regulated process, which supports mitochondrial bioenergetics and sustains lysosomal acidity. Iron and pH dysregulation synergize to drive ferroptosis, lipid peroxidation, and neurotoxicity. Emerging studies link lysosomal deacidification and iron dyshomeostasis to the pathogenesis of major neurodegenerative diseases. These mechanisms collectively shape neuronal resilience, survival, and aging trajectories. This review integrates recent insights into how TLDc proteins coordinate organellar pH regulation and iron homeostasis and discusses how disruption of these interconnected pathways contributes to age-related neurodegeneration. - Source: PubMed
Publication date: 2026/09/01
Ghufran Mohammad SajidSoni PriyankaThomas Bobby - Transmembrane protein 175 (TMEM175) is a lysosomal proton-activated and proton-selective channel critical for regulating lysosomal membrane potential and acidity. However, its role in cardiomyocyte physiological and stress response remains unclear. Here, we investigated the function of TMEM175 in mitochondrial homeostasis using H9c2 cardiomyocytes and neonatal rat ventricular myocytes (NRVMs) under physiological conditions and during hydrogen peroxide (HO)-induced oxidative stress. Under physiological conditions, genetic knockout of TMEM175 impaired mitochondrial respiration, reduced mitochondrial superoxide, and attenuated autophagic clearance. In contrast, under HO-induced stress, TMEM175 deletion significantly alleviated mitochondrial dysfunction and cell death, despite autophagic flux being primarily stalled at the degradation stage. Mechanistically, TMEM175 deficiency activated AMP-activated protein kinase (AMPK), and silencing AMPK reversed the cytoprotective effects of TMEM175 deletion against HO injury. Pharmacological inhibition of TMEM175 with 2-phenylpyridin-4-ylamine (2-PPA) in H9c2 and NRVMs recapitulated key phenotypes observed in genetic knockout models. Furthermore, 2-PPA improved cardiac function and attenuated histopathological injury in myocardial infarction mice. Together, these findings reveal a dual role for TMEM175: it maintains lysosomal-mitochondrial communication under basal conditions, yet its inhibition protects against oxidative stress primarily through AMPK activation. This study identifies TMEM175 as a novel lysosomal regulator of cardiac mitochondrial resilience and highlights its potential role in the cellular response to oxidative injury in cardiomyocytes. - Source: PubMed
Publication date: 2026/08/18
Li QingliuHu NanZhao LimeiZhang ShaoxuanMeng LuluZhou JinyuLi QiujieLei FuchengYang XiaotongHu MeiqinZhu HuaHang PengzhouZhao Jing - Microglia, the resident immune cells of the central nervous system (CNS), maintain brain homeostasis and respond to pathological insults. Microglial dysfunction has been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Impaired lysosomal function, particularly defective lysosomal acidification, leads to the accumulation of undegraded material, thereby promoting neuroinflammation and neuronal damage. - Source: PubMed
Publication date: 2026/08/03
Jaganathan RavindranVijayakumar SrilakshmiChen YinchiYe JiaxiBakthavatchalam PugazhandhiWankhar DapkuparYang ChuanbinIyaswamy AshokLi Min