Fig. 3.

Aβ, ABAD and mitochondria: modes of interactions. a Under normal conditions, ABAD is responsible of the reversible oxido/reduction of linear alcohols and steroids, such as the reversible conversion from oestradiol to oestrone. Its potential function as an RNAse P could also be important for the good functioning of the mitochondrial ETC. b Under AD-relevant pathological conditions, Aβ can directly bind the mitochondrial enzyme ABAD, changing the configuration of the enzyme which seems to inhibit its activity and creates an imbalance between oestradiol and oestrone. Aβ-induced ABAD misfolding can impact ETC functioning and increase, directly or indirectly, ROS production, which lead to cell death. c In the presence of AG18051 (AG), the binding of Aβ to ABAD is inhibited, normalizing oestradiol level, ROS production, ETC activity, and improves cell survival. ABAD Aβ-binding alcohol dehydrogenase, IMM inner mitochondrial membrane, OMM outer mitochondrial membrane