{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSideroflexin 1 (SFXN1) is an integral protein of the inner mitochondrial membrane that principally functions as a transporter of serine into mitochondria, thereby fueling one‐carbon metabolism. In this essential biochemical pathway, imported serine is converted into glycine and formate, supporting nucleotide and purine synthesis. Moreover, loss of SFXN1 impairs glycine production and overall mitochondrial one‐carbon metabolism, underlining its pivotal role in cellular anabolic processes (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical metabolic function, SFXN1 contributes to mitochondrial respiratory efficiency by influencing complex III biogenesis, activity, and assembly. It supports heme and α‐ketoglutarate metabolism, and its deficiency disrupts coenzyme Q levels, thereby compromising the electron transport chain independent of its role in one‐carbon metabolism (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond mitochondrial bioenergetics, a circular RNA derived from the SFXN1 locus (CircSFXN1) has been implicated in the pathogenesis of preeclampsia. This circRNA modulates the behavior of trophoblasts and endothelial cells by recruiting sFLT1, which in turn alters cell invasion and angiogenesis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSFXN1 also plays a significant role in cancer biology. In lung adenocarcinoma, elevated SFXN1 expression promotes cell proliferation, migration, and invasion while suppressing apoptosis via activation of the mTOR signaling pathway, establishing it as an independent prognostic marker for the disease (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " \n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSimilarly, in triple‐negative breast cancer, upregulated SFXN1 fosters tumor growth and metastasis by inhibiting TOLLIP‐mediated autophagic degradation of the oncogenic protein CIP2A, consequently activating downstream PP2A/AKT signaling. In non‐viral hepatocellular carcinoma, reduced SFXN1 expression correlates with diminished lipid accumulation and reactive oxygen species production, impacting tumorigenic potential and patient outcomes (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings demonstrate that SFXN1 is a multifaceted protein: it serves as a mitochondrial serine transporter essential for one‐carbon metabolism, supports proper respiratory chain function through effects on complex III and related metabolic pathways, and modulates diverse cellular processes that influence cancer progression. This broad spectrum of functions underscores its potential as both a prognostic biomarker and a promising therapeutic target, particularly in malignancies such as lung adenocarcinoma (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nora Kory, Gregory A Wyant, Gyan Prakash, et al. 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