Florian Bonn

TL;DR: This work identifies AFG3L2 as a novel cause of dominant neurodegenerative disease and indicates a previously unknown role for this component of the mitochondrial protein quality control machinery in protecting the human cerebellum against neurodegenersation.

TL;DR: An early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy is reported.

TL;DR: It is demonstrated that the formation of a tightly folded domain harbouring a conserved CxxC‐X9‐CxxC sequence motif halts degradation initiated from the N‐terminus and triggers the release of mature MrpL32, explaining the need for post‐translocational processing by the m‐AAA protease rather than co‐transLocational cleavage by the general mitochondrial processing peptidase.

TL;DR: It is established that mammalian m-AAA proteases can act as processing enzymes in vivo and overlapping activities of Afg3l1 and Afg 3l2 are revealed, of relevance for the pathogenesis of neurodegenerative disorders associated with mutations in different m- AAA protease subunits.

TL;DR: It is demonstrated that the newly identified paraplegin variants perturb the proteolytic function of hetero‐oligomeric m‐AAA protease, which will facilitate the interpretation of genetic data for SPG7.