Reactome | AFG3L2 degrades mitochondrial inner membrane proteins

AFG3L2 degrades mitochondrial inner membrane proteins

Stable Identifier

R-HSA-9839113

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

mitochondrial inner membrane

ReviewStatus

5/5

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AFG3L2 degrades mitochondrial inner membrane proteins

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AFG3L2 (m-AAA+) is a hexameric zinc metalloprotease that is anchored in the mitochondrial inner membrane and protrudes into the mitochondrial matrix (Koppen et al. 2007, Puchades et al. 2019). AFG3L2 is able to assemble as homohexamers or as heterohexamers with its paralog SPG7 (Paraplegin) (Atorino et al. 2003). Each AFG3L2 subunit has a membrane-proximal ATPase domain that unfolds proteins and a membrane-distal protease domain (Puchades et al. 2019). The substrate protein threads through the ATPase spiral of the AFG3L2 hexamer (Puchades et al. 2019) and is processively translocated and degraded in an ATP-dependent manner. AFG3L2 preferentially cleaves peptide bonds on the N-terminal side of hydrophobic residues (Ding et al. 2018). AFG3L2 binds and degrades specific inner membrane proteins, including COX5A (Cesnekova et al. 2018), MT-CO1 (Cesnekova et al. 2018), and MT-ATP6 (Richter et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
31327635	Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease Glynn, SE, Wiseman, RL, Song, A, Lander, GC, Puchades, C, Ding, B	Mol Cell	2019
17101804	Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia Casari, G, Rugarli, EI, Metodiev, MD, Langer, T, Koppen, M	Mol Cell Biol	2007
29932645	Dissecting Substrate Specificities of the Mitochondrial AFG3L2 Protease Glynn, SE, Ding, B, Rampello, AJ, Martin, DW	Biochemistry	2018
26504172	Quality control of mitochondrial protein synthesis is required for membrane integrity and cell fitness Battersby, BJ, Lahtinen, T, Suomi, F, Marttinen, P, Richter, U	J Cell Biol	2015
30544562	Loss of Mitochondrial AAA Proteases AFG3L2 and YME1L Impairs Mitochondrial Structure and Respiratory Chain Biogenesis Cesnekova, J, Stiburek, L, Hansikova, H, Rodinova, M, Zeman, J	Int J Mol Sci	2018