accepted manuscript

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complex I activity. Discrepant reports on complex I activities in PD patients may best
be explained by methodological issues, in particular sample preparation and assay
technique. It is also conceivable that variations in the extent of complex I deficiency
or differences between brain and peripheral tissues reflect the fact that PD is not a
uniform entity, but rather an etiologically and pathologically heterogeneous
syndrome.
1.1.2. Complex I and oxidative stress
Transport of electrons through complexes I to IV in the inner mitochondrial
membrane involves a series of coupled redox reactions, which provide the energy to
create a proton gradient across the inner mitochondrial membrane. Reducing
equivalents from catabolic processes enter the electron transport chain (ETC) as
NADH (at complex I) or FADH2 (at complex II). Electrons from NADH or FADH2
are passed on in a stepwise fashion until they reduce oxygen to water at complex IV.
The movement of protons from the mitochondrial matrix to the intermembrane space
creates an electrochemical gradient across the inner mitochondrial membrane. The
electrochemical gradient, also called proton-motive force, is composed of a pH
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gradient (ΔpH) and an electrical potential (Δψ) and drives ATP synthesis from ADP
as protons re-enter the matrix through the ATP synthase (complex V). The whole
process is called oxidative phosphorylation.
Complex I is the main gateway for electrons to enter the respiratory chain
(rev. in [60, 61]). It consists of 14 central and up to 32 accessory subunits, which form
an L-shaped complex with a membrane arm and a peripheral arm protruding into the
mitochondrial matrix. Seven hydrophobic subunits forming the membrane central
core are encoded by mitochondrial (mt) DNA. Complex I catalyzes the electron
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