The respiratory chain plays a central role in energy
metabolism of the cell. It is localized in mitochondria, the cell´s own power
plants. In a new study, researchers from
Goethe University, the Max Planck Institute of Biophysics and the University of
Helsinki have determined the high-resolution structure of a central component
of the respiratory chain, mitochondrial complex I, and simulated its dynamics on
the computer. These findings both support basic research and enhance our
understanding of certain neuromuscular and neurodegenerative diseases that are
linked with mitochondrial dysfunction.
FRANKFURT. All
vital processes require a constant supply of energy. In the cell, the
chemically “charged" molecule ATP is the main provider of this energy. The ATP power
packs are produced, among others, in specialised small organs (“organelles") of
the cell, the mitochondria.
There, the protein complexes of the respiratory
chain pump hydrogen ions (protons with a positive charge) from one side of the
inner mitochondrial membrane to the other (“uphill"), creating a chemical
concentration gradient and an electrical voltage. The protons “flow downhill" along
this electrochemical gradient through a kind of turbine that generates useful
energy for the cell in the form of ATP.
One of the proton pumps in the first step
of the process is a large, L-shaped biomolecule, mitochondrial complex I (in
short: complex I). Its horizontal arm is anchored in the membrane. The vertical
arm binds the electron carrier molecule NADH, which is produced during
metabolic breakdown of sugar and other nutrients. Complex I catalyses the transfer
of electrons from NADH to ubiquinone (Q10), and the energy released in this
reaction is used to drive the proton pump.
The research team from Goethe University
and the Max Planck Institute of Biophysics in Frankfurt used cryo-electron
microscopy to determine the 3D structure of complex I at high resolution. The researchers
were able to show that water molecules in the protein structure play an
important role for establishing proton translocation pathways.
The high-resolution structural data
enabled colleagues at the University of Helsinki to conduct extensive computer
simulations, which show the dynamics of the protein structure during its
catalytic cycle.
Dr Janet Vonck from the Max Planck
Institute of Biophysics explains: “Our study delivers new insights into how a
molecular machine in biological energy conversion works." Professor Volker Zickermann
from the Institute of Biochemistry II at Goethe University says: “This
knowledge can contribute to a better understanding of certain mitochondrial
diseases, such as loss of vision in Leber hereditary optic neuropathy."
Publication:
Kristian Parey, Jonathan Lasham, Deryck J.
Mills, Amina Djurabekova, Outi Haapanen, Etienne Galemou Yoga, Hao
Xie, Werner Kühlbrandt, Vivek Sharma, Janet Vonck, Volker Zickermann:
High-resolution structure and dynamics of mitochondrial complex I – Insights
into the proton pumping mechanism. Sci Adv. 2021 Nov 12;7 (46) https://www.science.org/doi/10.1126/sciadv.abj3221
An
image can be
downloaded under: https://www.uni-frankfurt.de/109657054
Caption:
A bit like a
boot: The L-shaped structure of mitochondrial complex I at a resolution of 2.1 Ångström (0.00000021
millimetres), captured with a cryo-electron microscope. Image: Janet Vonck, MPI of Biophysics
Further
information
Professor Volker Zickermann
Institute of Biochemistry II
Goethe University, Frankfurt am Main
Tel.: +49 (0)69 798-29575
zickermann@med.uni-frankfurt.de
Dr Janet Vonck
Max Planck Institute of
Biophysics, Frankfurt am Main
Phone: +49 (0)69 6303-3004
janet.vonck@biophys.mpg.de
