The mitochondrial protease AFG3L2 is essential for axonal development.
Document Type
Article
Publication Date
2008
Keywords
Amino-Acid-Sequence, Animals-Newborn, Axons, Mice-Mutant-Strains, Mitochondria, Mitochondrial-Proteins, Molecular-Sequence-Data
First Page
2827
Last Page
2836
JAX Source
J Neurosci 2008 Mar; 28(11):2827-36.
Abstract
The mitochondrial metalloprotease AFG3L2 assembles with the homologous protein paraplegin to form a supracomplex in charge of the essential protein quality control within mitochondria. Mutations of paraplegin cause a specific axonal degeneration of the upper motoneuron and, therefore, hereditary spastic paraplegia. Here we present two Afg3l2 murine models: a newly developed null and a spontaneous mutant that we found carrier of a missense mutation. Contrasting with the mild and late onset axonal degeneration of paraplegin-deficient mouse, Afg3l2 models display a marked impairment of axonal development with delayed myelination and poor axonal radial growth leading to lethality at P16. The increased severity of the Afg3l2 mutants is explained by two main molecular features that differentiate AFG3L2 from paraplegin: its higher neuronal expression and its versatile ability to support both hetero-oligomerization and homo-oligomerization. Our data assign to AFG3L2 a crucial role by linking mitochondrial metabolism and axonal development. Moreover, we propose AFG3L2 as an excellent candidate for motoneuron and cerebellar diseases with early onset unknown etiology.
Recommended Citation
Maltecca F,
Aghaie A,
Schroeder DG,
Cassina L,
Taylor BA,
Phillips SJ,
Malaguti M,
Previtali S,
Guenet JL,
Quattrini A,
Cox GA,
Casari G.
The mitochondrial protease AFG3L2 is essential for axonal development. J Neurosci 2008 Mar; 28(11):2827-36.