Minerva Fast Track Group

Lea Dietrich

There are two reasons why we are fascinated by the human brain. Firstly, it’s incredible complexity and secondly, its vast energy requirements. Billions of neurons are powered by mitochondria, which enable neuronal growth, signal transmission, and synaptic plasticity. Mitochondria rely on the finely tuned interplay of proteins in the oxidative phosphorylation machinery to supply cells with sufficient adenosine triphosphate (ATP), which drives and maintains vital cellular processes. Neurons have a highly specialized structure, including a cell body containing the nucleus — the control center of each cell — an axon that transmits information to other cells and dendrites that receive and relay information. The specific energy requirements of each part of the nerve cell raise the question of the extent to which mitochondria are subject to local adaptation.

Our goal is to explore and understand these local adaptations in mitochondrial architecture, and to examine how they are reflected at the molecular level. Specifically, we are interested in the relationship between structure and function, particularly in relation to the architecture of the inner mitochondrial membrane and the organization of the proteins it contains.

We address this question by using in situ structural biology. By obtaining an undisturbed view inside cells or inside tissue we can address the following questions :

What is the structure and arrangement of the oxidative phosphorylation machinery inside neurons?
Do they interact with each other and with other proteins?
Does the structure and arrangement of the proteins change depending on the location and thus energy requirements of the mitochondria within a single neuron and throughout the brain?

The group is embedded within the Department of Synaptic Plasticity led by Erin Schuman. This provides us with the exciting opportunity to incorporate our results into a framework of complementary methods.

Selected Publications

*These authors contributed equally
‡ Co-corresponding author

DOI Dietrich L. ‡, Agip A.-N. A., Kunz C., Schwarz A., Kühlbrandt W., “In situ structure and rotary states of
mitochondrial ATPsynthase in whole Polytomella cells”, Science 385,1086-1090 (2024)

DOI Sanchez, R.M., Zhang, Y., Chen, W., Dietrich L., Kudryashev M., “Subnanometer-resolution structure determination in situ by hybrid subtomogram averaging - single particle cryo-EM” Nat Commun 11, 3709 (2020)

DOI Faelber, K.*, Dietrich, L.*, et al. “Structure and assembly of the mitochondrial membrane remodelling GTPase Mgm1.” Nature 571, 429–433 (2019)

Header image credits: (c) Max Planck Institute of Biophysics / P. Ornelas