Reactome | AFG3L2 binds mitochondrial matrix proteins

AFG3L2 binds mitochondrial matrix proteins

Stable Identifier

R-HSA-9839149

Type

Reaction [binding]

Species

Homo sapiens

Compartment

mitochondrial matrix, mitochondrial inner membrane

ReviewStatus

5/5

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AFG3L2 binds mitochondrial matrix 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 binds, unfolds, and degrades mitochondrial matrix proteins, including steroidogenic acute regulatory protein (STAR) (Bahat et al. 2014), the ribosomal subunit MRPL32 (Koppen et al. 2007, Ding et al. 2018), and the peripheral inner membrane protein ATP5F1A (Cesnekova et al. 2018).
Mutations in AFG3L2 have been linked with development of spinocerebellar ataxia type 28 (SCA28), an autosomal dominant neurodegenerative disease (Tulli et al. 2019).

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 Puchades, C, Ding, B, Song, A, Wiseman, RL, Lander, GC, Glynn, SE	Mol Cell	2019
17101804	Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia Koppen, M, Metodiev, MD, Casari, G, Rugarli, EI, Langer, T	Mol Cell Biol	2007
29932645	Dissecting Substrate Specificities of the Mitochondrial AFG3L2 Protease Ding, B, Martin, DW, Rampello, AJ, Glynn, SE	Biochemistry	2018
30544562	Loss of Mitochondrial AAA Proteases AFG3L2 and YME1L Impairs Mitochondrial Structure and Respiratory Chain Biogenesis Cesnekova, J, Rodinova, M, Hansikova, H, Zeman, J, Stiburek, L	Int J Mol Sci	2018
24422629	StAR enhances transcription of genes encoding the mitochondrial proteases involved in its own degradation Bahat, A, Perlberg, S, Melamed-Book, N, Lauria, I, Langer, T, Orly, J	Mol Endocrinol	2014