3.A.29.  The Mitochondrial Inner Membrane i-AAA Protease Complex (MIMP) Familly 

The mitochondrial inner membrane i-AAA protease supercomplex is required for mitochondrial inner membrane protein insertion, degradation and turnover. It is important to maintain the integrity of the mitochondrial compartment and is required both for the degradation of unassembled subunit 2 of cytochrome c oxidase (COX2) and for efficient assembly of the mitochondrial respiratory chain. It binds unfolded substrates in an ATPase-independent manner; binding of folded COX2, a physiological substrate, requires an active ATPase but when COX2 is destabilized an active ATPase is no longer necessary.  Central pore mutants of Yta11 (Yme1, OSD1) have been isoated (Graef and Langer 2006; Dunn et al. 2006).

Protein complexes involved in respiration, ATP synthesis, and protein import reside in the mitochondrial inner membrane. The m-AAA protease, a conserved hetero-hexameric AAA (ATPase associated with diverse cellular activities) protease, composed of the Yta10, Yta11 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates the dislocation of membrane-embedded substrates, including foreign transmembrane (TM) segments. The Yta10 TMS2 domain is essential for membrane dislocation for only a subset of substrates, whereas the Yta12 TMS2 domain is essential for membrane dislocation for all tested substrates, suggesting different roles of the TM domains in these two m-AAA protease subunits. m-AAA protease-mediated membrane dislocation was impaired in the presence of a large downstream hydrophilic moiety in a membrane substrate, suggesting that the m-AAA protease cannot dislocate large hydrophilic domains across the membrane.  Thus, membrane dislocation depends on the TMSs (Lee et al. 2017).


This family belongs to the AAA-ATPase Superfamily.



Dunn, C.D., M.S. Lee, F.A. Spencer, and R.E. Jensen. (2006). A genomewide screen for petite-negative yeast strains yields a new subunit of the i-AAA protease complex. Mol. Biol. Cell 17: 213-226.

Graef, M. and T. Langer. (2006). Substrate specific consequences of central pore mutations in the i-AAA protease Yme1 on substrate engagement. J Struct Biol 156: 101-108.

Lee, S., H. Lee, S. Yoo, and H. Kim. (2017). Molecular insights into the-AAA protease-mediated dislocation of transmembrane helices in the mitochondrial inner membrane. J. Biol. Chem. 292: 20058-20066.

Nargund, A.M., C.J. Fiorese, M.W. Pellegrino, P. Deng, and C.M. Haynes. (2015). Mitochondrial and nuclear accumulation of the transcription factor ATFS-1 promotes OXPHOS recovery during the UPR(mt). Mol. Cell 58: 123-133.

Nargund, A.M., M.W. Pellegrino, C.J. Fiorese, B.M. Baker, and C.M. Haynes. (2012). Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 337: 587-590.

Pellegrino, M.W., A.M. Nargund, N.V. Kirienko, R. Gillis, C.J. Fiorese, and C.M. Haynes. (2014). Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection. Nature 516: 414-417.


TC#NameOrganismal TypeExample

The mitochondrial i-AAA protease complex involved in inner membrane insertion and turnover.  It consists of Yta10, Yta11 and Yta12 (Lee et al. 2017).

Protease complex of Saccharomyces cerevisiae
Yta10, Afg3 of 761 aas with 2 TMSs
Yta11, Yme1, Osd1, of 747 aas and 2 TMSs
Yta12, RCA1, of 825 aas


Mitochondrial AAA protease complex of two enzymes, Yta10/12 (Afg3-like or Spg-7) and Yta11 (Ymel-1). It is a mitochondrial ATP-dependent metalloprotease complex mediating degradation of non-assembled mitochondrial inner membrane proteins and necessary for the assembly of the mitochondrial respiratory chain and ATPase complexes. It functions both in post-translational assembly and in the turnover of mistranslated or misfolded polypeptides (Nargund et al. 2012, Pellegrino et al. 2014, Nargund et al. 2015).

Protease complex of Caenorhabditis elegans
Spg-7 (Ata10/12), 782 aas and 2 TMSs
Yme1 (Ata11; Ymel-1), 723 aas and 1 TMS