Figure 1.

Mitochondrial dysfunction in Alzheimer's disease (AD) and Parkinson's disease (PD). Mitochondrial dysfunction has been implicated in the etiology of AD and PD. In AD, it has been shown that amyloid β peptide (Aβ) impairs the activity of respiratory chain complex IV, leading to increased reactive oxygen species (ROS) levels and ATP depletion. Moreover, mitochondrial DNA (mtDNA) mutations have also been implicated in mitochondrial dysfunction that occurs in AD. PD is associated with an impairment of mitochondrial complex I activity. It has been demonstrated that the pharmacological inhibition of this complex with rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes degeneration of the nigral dopaminergic neurons and PD symptoms in in vivo models. The familial forms of PD are associated with mutations in leucine-rich repeat kinase 2 (LRRK2), α-synuclein, parkin, DJ1, and PTEN-induced putative kinase 1 (PINK1), these proteins being associated with the mitochondrial outer membrane (OM) and involved in ROS production or defense. High temperature requirement A2 (HtrA2) is another protein that is mutated in familial PD and is localized in the intermembrane space (IMS) of mitochondria. ADP, adenosine diphosphate; Cyt c, cytochrome c; IM, inner membrane; NAD⁺, oxidized nicotinamide adenine dinucleotide; NADH, reduced nicotinamide adenine dinucleotide; H⁺, proton.