{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nATAD3A is emerging as a central regulator of mitochondrial architecture and biogenesis during early development and cellular homeostasis. Loss‐of‐function studies in mice revealed that ATAD3A is critical for proper trophoblast differentiation and mitochondrial biogenesis, as its absence early after implantation leads to embryonic lethality."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Complementary analyses have established that ATAD3 is expressed in multiple isoforms in both rodent and human tissues, suggesting finely tuned and context‐dependent roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, ATAD3A facilitates mitochondria–endoplasmic reticulum (ER) contact site formation which is important for efficient steroidogenesis in Leydig cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and it has been shown to interact with key mediators of mitochondrial nucleoid maintenance and DNA repair such as Fancd2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn differentiated tissues, perturbation of ATAD3A function leads to severe mitochondrial dysfunction that critically impacts cell fate and survival. Targeted deletion of Atad3a in hematopoietic cells causes hyperactivation of mitophagy and skewed stem cell differentiation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while skeletal muscle–specific Atad3 knockout results in drastic alterations in mitochondrial cristae structure and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In models of neurodegenerative disorders, deacetylation-driven dimerization of ATAD3A crucially facilitates Drp1-mediated mitochondrial fragmentation and subsequent mtDNA destabilization, linking it to Huntington's disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, neuronal-specific deletion of Atad3 results in profound encephalopathy associated with early disruptions in inner mitochondrial membrane organization"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and ATAD3A oligomerization has been implicated in perturbing cholesterol metabolism and APP processing in Alzheimer's disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nATAD3A also coordinates interorganelle communication in a tissue-specific manner to preserve cellular bioenergetics. Its role in maintaining ER–mitochondria contacts is critical in cardiac tissue, where ATAD3A prevents mitochondrial calcium overload and supports mitochondrial function during stress"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In addition, modulation of ATAD3 levels directly influences mitochondrial biogenesis during adipogenesis, with overexpression accelerating the differentiation and lipogenic process in adipocyte cell models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tobias Goller, Ursula K Seibold, Elisabeth Kremmer, et al. 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