ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly

Tania Arguello, Susana Peralta, Hana Antonicka, Gabriel Gaidosh, Francisca Diaz, Ya Ting Tu, Sofia Garcia, Ramin Shiekhattar, Antonio Barrientos, Carlos T Moraes

Research output: Contribution to journalArticlepeer-review


The ATPase Family AAA Domain Containing 3A (ATAD3A), is a mitochondrial inner membrane protein conserved in metazoans. ATAD3A has been associated with several mitochondrial functions, including nucleoid organization, cholesterol metabolism, and mitochondrial translation. To address its primary role, we generated a neuronal-specific conditional knockout (Atad3 nKO) mouse model, which developed a severe encephalopathy by 5 months of age. Pre-symptomatic mice showed aberrant mitochondrial cristae morphogenesis in the cortex as early as 2 months. Using a multi-omics approach in the CNS of 2-to-3-month-old mice, we found early alterations in the organelle membrane structure. We also show that human ATAD3A associates with different components of the inner membrane, including OXPHOS complex I, Letm1, and prohibitin complexes. Stochastic Optical Reconstruction Microscopy (STORM) shows that ATAD3A is regularly distributed along the inner mitochondrial membrane, suggesting a critical structural role in inner mitochondrial membrane and its organization, most likely in an ATPase-dependent manner.

Original languageEnglish (US)
Article number110139
JournalCell Reports
Issue number12
StatePublished - Dec 21 2021


  • ATAD3
  • cardiolipin
  • cristae
  • inner membrane
  • mitochondria

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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