By: Thomas Langer, Institute for Genetics and CECAD Research Center, University of Cologne

Mitochondrial Proteases and Neurodegentation
Mitochondrial proteases ensure protein quality control within the organelle and mediate regulated proteolytic
reactions important for mitochondrial function, integrity and homeostasis, such as protein synthesis,
phospholipid trafficking, mitochondrial dynamics, mitophagy and apoptosis. Impaired or dysregulated
function of mitochondrial proteases is associated with ageing and with many pathological conditions,
such as neurodegenerative disorders, metabolic syndromes and cancer. This is exemplified by
m-AAA proteases which form hexameric proteolytic complexes in the mitochondrial inner membrane.
 Mutations in m-AAA protease subunits are associated with spinocerebellar ataxia (SCA28) and
hereditary spastic paraplegia (HSP), respectively, as well as other neurological syndromes (SPAX5).
In order to unravel the molecular basis for neuronal loss and the neuron-specific effects of mutations in
m-AAA proteases, we defined the neuronal interactome of m-AAA proteases in mouse. Functional studies
on newly identified interactors of m-AAA proteases will be discussed.