Amyloid precursor protein and mitochondria

• Published in: Current opinion in neurobiology Vol. 78; p. 102651
• Main Authors: Strope, Taylor A., Wilkins, Heather M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2023
• Subjects: Alzheimer Disease; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein; Amyloid Precursor Protein Secretases - metabolism; Bioenergetics; Humans; Mitochondria; Mitochondria - metabolism; γ-secretase; Mitochondria; Bioenergetics; γ-secretase; Alzheimer's disease; Amyloid precursor protein
• ISSN: 0959-4388; 1873-6882; 1873-6882
• DOI: 10.1016/j.conb.2022.102651

Amyloid Precursor Protein (APP) processing to amyloid beta (Aβ) is a major hallmark of Alzheimer's disease (AD). The amyloid cascade hypothesis postulates that Aβ accumulation and aggregation causes AD, however many therapeutics targeting Aβ have failed recently. Decades of research describe metabolic deficits in AD. Mitochondrial dysfunction is observed in AD subjects within the brain and systemically. APP and γ-secretase are localized to mitochondria. APP can be processed within mitochondria and its localization to mitochondria affects function. Here we discuss the evidence showing APP and γ-secretase localize to mitochondria. We also discuss the implications for the function of APP and its cleavage products in regulating mitochondrial function. •Amyloid Precursor protein (APP) localizes to mitochondria and associated membranes.•γ-secretase localizes to mitochondria and participates in APP processing.•Changes to APP expression or mitochondrial localization affect mitochondrial function.