2024年5月23日 · In this Article, we identify the major mtDNA-bound protein TFAM as an autophagy receptor for nucleoid clearance. We demonstrate that TFAM interacts with microtubule-associated protein 1 light...

在最新的这项研究中，研究人员利用缺乏线粒体DNA复制所需关键蛋白 TFAM （线粒体转录因子A，mitochondrial transcription factor A）的小鼠模型，发现线粒体DNA缺失后，会导致炎性小体激活缺陷。如果将体外合成的氧化的线粒体DNA转移到缺乏TFAM的巨噬细胞中，则会发现 ...

2020年12月3日 · Lipopolysaccharide (LPS) increases extramitochondrial but not intramitochondrial TFAM abundance. LPS stimulation of PBMCs from healthy volunteers before and after 0.5, 4, 24, and 48...

2018年7月25日 · Transfection of synthetic D-loop ox-mtDNA into lipopolysaccharide (LPS)-primed TfamΔMye BMDMs induced IL-1β production without any known NLRP3 activator (Fig. 1a).

We found that diverse NLRP3 inflammasome activators rapidly stimulated uniporter-mediated calcium uptake to open mitochondrial permeability transition pores (mPTP) and trigger VDAC oligomerization. This occurred independently of mtDNA or reactive oxygen species, which induce Ox-mtDNA generation.

2017年1月1日 · The expression and the location of toll-like receptor 4 (TLR4) and mitochondrial transcription factor A (TFAM) were determined to reveal possible mechanisms. LPS-treated sperm showed significant reduction in motility (P < 0.05) and viability (P < 0.05).

TFAM reduced ROS and P38MAPK levels by inhibiting toll-like receptor 4 (TLR4) expression, ultimately inhibiting inflammation and repairing mtDNA. Conclusions: Our results indicate that TFAM repairs mtDNA by blocking the TLR4/ROS/P38MAPK signaling pathway in inflammatory cells, thereby repairing septic tubular epithelial cells, and TFAM may ...

Overexpression of TFAM reversed the effects of C/EBPβ deficiency on pyroptosis. Knockdown of C/EBPβ could inhibit NLRP3 inflammasome-mediated caspase-1 signaling pathway by inactivating TFAM/RAGE pathway. It was further confirmed in the AKI mice that C/EBPβ and TFAM promoted AKI by activating NLRP3-mediated pyroptosis.

2011年12月1日 · Six to 48 h after LPS administration (5 mg/kg), liver mtDNA levels, respiratory complex I activity, and adenosine triphosphate (ATP) contents were decreased. In addition, LPS increased interferon-β concentration and decreased mitochondrial transcription factor A (Tfam) mRNA, Tfam protein, and mtDNA-encoded mRNAs.

该研究发现线粒体转录因子A (TFAM) -一种结合线粒体DNA (mtDNA)的蛋白质-通过自噬酶体途径 (称之为核吞噬)与自噬蛋白LC3相互作用，帮助消除泄漏的mtDNA。 TFAM包含一个称为LC3相互作用区 (LIR)基序的分子邮政编码，使这种结合成为可能。 虽然突变TFAM的LIR基序不会影响其正常的线粒体功能，但更多的mtDNA积聚在细胞质中，激活炎症信号通路。 因此，TFAM介导泄漏mtDNA的自噬清除以限制炎症。 确定这一机制有助于了解细胞如何利用自噬机制选择性地靶 …