1. The mitochondrial protease AFG3L2 is essential for axonal development.
- Author
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Maltecca F, Aghaie A, Schroeder DG, Cassina L, Taylor BA, Phillips SJ, Malaguti M, Previtali S, Guénet JL, Quattrini A, Cox GA, and Casari G
- Subjects
- ATP-Dependent Proteases, ATPases Associated with Diverse Cellular Activities, Adenosine Triphosphatases genetics, Amino Acid Sequence, Animals, Animals, Newborn, Axons pathology, Axons physiology, Mice, Mice, Mutant Strains, Mitochondria genetics, Mitochondria pathology, Mitochondrial Proteins genetics, Molecular Sequence Data, Adenosine Triphosphatases biosynthesis, Axons enzymology, Mitochondria enzymology, Mitochondrial Proteins biosynthesis
- 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.
- Published
- 2008
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