Mossmann D Vögtle FN Taskin AA Teixeira PF Ring J Burkhart JM Burger N Pinho CM Tadic J Loreth D Graff C Metzger F Sickmann A Kretz O Wiedemann N Zahedi RP Madeo F Glaser E Meisinger C 2014 Most mitochondrial proteins possess N-terminal presequences that are required for targeting and import into the organelle. Upon import, presequences are cleaved off by matrix processing peptidases and subsequently degraded by the peptidasome Cym1/PreP, which also degrades Amyloid-beta peptides (Aβ). Here we find that impaired turnover of presequence peptides results in feedback inhibition of presequence processing enzymes. Moreover, Aβ inhibits degradation of presequence peptides by PreP, resulting in accumulation of mitochondrial preproteins and processing intermediates. Dysfunctional preprotein maturation leads to rapid protein degradation and an imbalanced organellar proteome. Our findings reveal a general mechanism by which Aβ peptide can induce the multiple diverse mitochondrial dysfunctions accompanying Alzheimer's disease. application/pdf https://sonar.ch/global/documents/189429 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cmet.2014.07.024 info:eu-repo/semantics/altIdentifier/pmid/25176146 info:eu-repo/semantics/openAccess Cell metabolism. - 2014 Alzheimer Disease Amyloid beta-Peptides Animals Brain Humans Metalloproteases Mice Mice, Inbred C57BL Mitochondria Mitochondrial Proteins Mutation Proto-Oncogene Proteins Reactive Oxygen Species Receptors, G-Protein-Coupled Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Serine Endopeptidases Superoxide Dismutase Amyloid-β peptide induces mitochondrial dysfunction by inhibition of preprotein maturation. http://purl.org/coar/resource_type/c_6501