ATPIF1 Blocking Peptide
- Known as:
- ATPIF1 Blocking Peptide
- Catalog number:
- 33r-3567
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- ATPIF1 Blocking Peptide
Related genes to: ATPIF1 Blocking Peptide
- Gene:
- ATP5IF1 NIH gene
- Name:
- ATP synthase inhibitory factor subunit 1
- Previous symbol:
- ATPIF1
- Synonyms:
- ATPI, IP, ATPIP, MGC1167, MGC8898
- Chromosome:
- 1p35.3
- Locus Type:
- gene with protein product
- Date approved:
- 2000-02-29
- Date modifiied:
- 2017-11-22
Related products to: ATPIF1 Blocking Peptide
Related articles to: ATPIF1 Blocking Peptide
- Breast cancer can be treated effectively with personalized, gene-targeted therapies due to its molecular and genetic differences. Our study aims to identify breast cancer-specific tumor suppressor genes related to autophagic cell death and discover new drugs that target these mechanisms, even if they are not breast cancer-specific. - Source: PubMed
Publication date: 2025/11/10
Duran Gizem AynaKiraz YağmurBaykara Deniz - Maintenance of the mitochondrial inner membrane potential (ΔΨm) is critical for many aspects of mitochondrial function. While ΔΨm loss and its consequences are well studied, little is known about the effects of mitochondrial hyperpolarization. In this study, we used cells deleted of ATP5IF1 (IF1), a natural inhibitor of the hydrolytic activity of the ATP synthase, as a genetic model of increased resting ΔΨm. We found that the nuclear DNA hypermethylates when the ΔΨm is chronically high, regulating the transcription of mitochondrial, carbohydrate and lipid genes. These effects can be reversed by decreasing the ΔΨm and recapitulated in wild-type (WT) cells exposed to environmental chemicals that cause hyperpolarization. Surprisingly, phospholipid changes, but not redox or metabolic alterations, linked the ΔΨm to the epigenome. Sorted hyperpolarized WT and ovarian cancer cells naturally depleted of IF1 also showed phospholipid remodeling, indicating this as an adaptation to mitochondrial hyperpolarization. These data provide a new framework for how mitochondria can impact epigenetics and cellular biology to influence health outcomes, including through chemical exposures and in disease states. - Source: PubMed
Publication date: 2025/04/29
Mori Mateus PratesLozoya Oswaldo ABrooks Ashley MBortner Carl DNadalutti Cristina ARyback BirgittaRickard Brittany POverchuk MartaRizvi ImranRogasevskaia TatianaHuang Kai TingHasan ProttoyHajnóczky GyörgySantos Janine H - OxPhos inhibitors have struggled to show a clinical benefit because of their inability to distinguish healthy from cancerous mitochondria. Herein, we describe an actionable bioenergetic mechanism unique to acute myeloid leukemia (AML) mitochondria. Unlike healthy cells that couple respiration to ATP synthesis, AML mitochondria support inner-membrane polarization by consuming ATP. Matrix ATP consumption allows cells to survive bioenergetic stress. Thus, we hypothesized AML cells may resist chemotherapy-induced cell death by reversing the ATP synthase reaction. In support, BCL-2 inhibition with venetoclax abolished OxPhos flux without affecting mitochondrial polarization. In surviving AML cells, sustained mitochondrial polarization depended on matrix ATP consumption. Mitochondrial ATP consumption was further enhanced in AML cells made refractory to venetoclax, consequential to down-regulations in the endogenous F-ATPase inhibitor ATP5IF1. Knockdown of ATP5IF1 conferred venetoclax resistance, while ATP5IF1 overexpression impaired F-ATPase activity and heightened sensitivity to venetoclax. These data identify matrix ATP consumption as a cancer cell-intrinsic bioenergetic vulnerability actionable in the context of BCL-2 targeted chemotherapy. - Source: PubMed
Publication date: 2025/04/09
Hagen James TMontgomery McLane MAruleba Raphael TChrest Brett RKrassovskaia PolinaGreen Thomas DPacheco Emely AKassai MikiZeczycki Tonya NSchmidt Cameron ABhowmick DebajitTan Su-FernFeith David JChalfant Charles ELoughran Thomas PLiles DarlaMinden Mark DSchimmer Aaron DShakil Md SalmanMcBride Matthew JCabot Myles CMcClung Joseph MFisher-Wellman Kelsey H - Human induced pluripotent stem cells (hiPSCs) are an invaluable tool to study molecular mechanisms on a human background. Culturing stem cells at an oxygen level different from their microenvironmental niche impacts their viability. To understand this mechanistically, dermal skin fibroblasts of 52 probands were reprogrammed into hiPSCs, followed by either hyperoxic (20 % O) or physioxic (5 % O) culture and proteomic profiling. Analysis of chromosomal stability by Giemsa-banding revealed that physioxic -cultured hiPSC clones exhibited less pathological karyotypes than hyperoxic (e.g. 6 % vs. 32 % mosaicism), higher pluripotency as evidenced by higher Stage-Specific Embryonic Antigen 3 positivity, higher glucose consumption and lactate production. Global proteomic analysis demonstrated lower abundance of several subunits of NADH:ubiquinone oxidoreductase (complex I) and an underrepresentation of pathways linked to oxidative phosphorylation and cellular senescence. Accordingly, release of the pro-senescent factor IGFBP3 and β-galactosidase staining were lower in physioxic hiPSCs. RNA- and ATAC-seq profiling revealed a distinct hypoxic transcription factor-binding footprint, amongst others higher expression of the HIF1α-regulated target NDUFA4L2 along with increased chromatin accessibility of the NDUFA4L2 gene locus. While mitochondrial DNA content did not differ between groups, physioxic hiPSCs revealed lower polarized mitochondrial membrane potential, altered mitochondrial network appearance and reduced basal respiration and electron transfer capacity. Blue-native polyacrylamide gel electrophoresis coupled to mass spectrometry of the mitochondrial complexes detected higher abundance of NDUFA4L2 and ATP5IF1 and loss of incorporation into complex IV or V, respectively. Taken together, physioxic culture of hiPSCs improved chromosomal stability, which was associated with downregulation of oxidative phosphorylation and senescence and extensive re-wiring of mitochondrial complex composition. - Source: PubMed
Publication date: 2024/09/11
Raabe JaniceWittig IlkaLaurette PatrickStathopoulou KonstantinaBrand TheresaSchulze ThomasKlampe BirgitOrthey EllenCabrera-Orefice AlfredoMeisterknecht JanaThiemann EllenLaufer Sandra DShibamiya AyaReinsch MarinaFuchs SigridKaiser JenniferYang JiaqiZehr SimonidaWrona Kinga MLorenz KristinaLukowski RobertHansen ArneGilsbach RalfBrandes Ralf PUlmer Bärbel MEschenhagen ThomasCuello Friederike - While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether FFo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called "reverse mode" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis. - Source: PubMed
Publication date: 2024/09/16
Brunetta Henver SJung Anna SValdivieso-Rivera Fernandode Campos Zani Stepheny CGuerra JoelFurino Vanessa OFrancisco AnneliseBerçot MarceloMoraes-Vieira Pedro MKeipert SusanneJastroch MartinMartinez Laurent OSponton Carlos HCastilho Roger FMori Marcelo ABartelt Alexander