SAFARI WITH AN ELECTRON GUN: VISUALIZATION OF PROTEIN AND MEMBRANE INTERACTIONS IN MITOCHONDRIA IN THE NATURAL ENVIRONMENT

Abstract

This paper presents new structural data about mitochondria using correlative light and electron microscopy and cryo-electron tomography (cryo-ET). These state-of-the-art structural biology methods allow the study of biological objects at nanometer scales in natural conditions. The non-invasiveness of these methods makes them comparable to observing animals in their natural environment on a safari. The paper highlights two areas of research that can only be accomplished using these methods. The study visualized the location of Aβ42 amyloid aggregates in relation to mitochondria to test a hypothesis for the development of mitochondrial dysfunction in Alzheimer’s disease. The results showed that Aβ42 aggregates do not interact with mitochondria, although some of them are closely located. Therefore, the study demonstrated that mitochondrial dysfunction is not directly influenced by aggregates on mitochondrial structure. The source of mitochondrial dysfunction should be investigated in other processes. Second unique area presented in this work is the high-resolution visualization of mitochondrial membranes and proteins in them. The analysis of cryo-ET data reveals toroidal holes in the lamellar structures of cardiac mitochondrial cristae, where ATP synthases are located. The study proposes a new mechanism for sorting and clustering protein complexes in the membrane based on topology. According to this mechanism, the position of oxidative phosohorylation system proteins in the membrane is determined by its curvature. High-resolution tomography expands and complements existing ideas about the structural and functional organization of mitochondria. This makes it possible to study the previously inaccessible structural interactions of proteins with each other and with membranes in vivo.