{"type": "root", "children": [{"type": "t", "text": "<div>\n "}, {"type": "p", "children": [{"type": "t", "text": "\n LONP1 is a highly conserved AAA+ mitochondrial protease that plays a central role in maintaining mitochondrial proteostasis and metabolic homeostasis. It recognizes and degrades oxidatively damaged, misfolded, or unassembled proteins within the mitochondrial matrix, thereby contributing to quality control and efficient respiratory complex remodeling. For instance, under hypoxic conditions LONP1 is induced as part of an adaptive response to promote the degradation of specific subunits (e.g. COX4‐1) and to facilitate a bioenergetic switch in respiration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, genetic ablation or functional insufficiency of LONP1 results in severe defects including impaired mitochondrial gene expression, accumulation of unprocessed proteins, disrupted oxidative phosphorylation and, ultimately, cellular dysfunction and embryonic lethality, highlighting its essential role in mitochondrial homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Dysregulation of LONP1 is implicated in diverse pathologies. Increased expression of LONP1 in several cancers promotes metabolic reprogramming, resistance to apoptosis, and enhanced reactive oxygen species (ROS) production that together support tumor cell proliferation and survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Conversely, diminished LONP1 activity leads to the accumulation of proteins such as TDP-43 in mitochondria, thereby exacerbating mitochondrial damage and contributing to neurodegenerative processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, mutations in LONP1 have been causally linked to developmental disorders such as CODAS syndrome, underscoring its critical function during embryogenesis and organ development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In other physiological contexts, LONP1 contributes to cardioprotection, where its upregulation during ischemic preconditioning helps preserve mitochondrial redox balance and reprograms bioenergetics under stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Overall, LONP1 is not only a key proteolytic enzyme that safeguards mitochondrial function through selective protein turnover, but it also interacts with chaperone systems and participates in stress responses that affect a wide range of cellular activities. Its multifaceted roles in proteolysis, chaperoning, and even mtDNA maintenance have established LONP1 as a central regulator in normal physiology and in disease states such as cancer, neurodegeneration, and developmental disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n</div>"}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ryo Fukuda, Huafeng Zhang, Jung-whan Kim, et al. 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