Research Klecker Group: Mitochondrial Ultrastructure
Mitochondria are particularly known for their function in energy metabolism, but they also play an important role in many other cellular processes. This extends beyond their contribution to several metabolic pathways and also includes cellular signaling and the regulation of apoptosis. A hallmark of mitochondria is their unique ultrastructure: The mitochondrial matrix is enclosed by two closely spaced membranes, which are separated from each other by the intermembrane space. The inner membrane is subdivided into the inner boundary membrane, which runs parallel to the outer membrane, and cristae, characteristic membrane invaginations which protrude into the interior of the organelle and adopt a tubular or lamellar shape in yeast. Cristae formation causes considerable curvature of the inner membrane, in particular at narrow tubular regions, bent edges of lamellar cristae, and the structures at which cristae and inner boundary membrane are connected, the crista junctions. The mitochondrial contact site and cristae organizing system (MICOS), ATP synthase dimers, and the GTPase Mgm1 have been identified as key factors involved in cristae maintenance (reviewed in Klecker and Westermann, 2021). However, our understanding of how cristae are formed and how this is regulated is still incomplete. We use budding yeast Saccharomyces cerevisiae as a model system to study the molecular machineries and processes that are involved in the shaping of the mitochondrial inner membrane.
Mitochondria are not rigid intracellular structures. Instead, they form an extended network that is constantly being reorganized by fusion, fission and transport events. Mitochondrial fusion and fission require coordinated remodeling of two membranes. Although much is known about the machineries that mediate fusion of both membranes and division of the outer membrane, there are many open questions about mitochondrial inner membrane division and cristae dynamics. We employ a combination of genetics and light and electron microscopy to investigate these processes.
Mechanisms determining morphology and dynamics of the mitochondrial inner membrane (DFG KL 2874/3-1)
Mitochondria adopt a characteristic ultrastructure. They are surrounded by a double membrane and the inner membrane folds into invaginations that are called cristae. The structure of both mitochondrial membranes is furthermore influenced by recurring fusion and fission events. In this project, we plan to study the molecular mechanisms that determine the dynamics and morphology of the mitochondrial inner membrane in yeast. Some components that play central roles in these processes have already been identified. Important examples are the MICOS complex, the F1FO-ATP synthase, and the GTPase Mgm1. However, a complete picture of all the factors that help to maintain mitochondrial ultrastructure is still missing. Furthermore, it is currently unknown whether also higher eukaryotes possess a separate machinery for the division of the inner membrane, as it is the case in some protists and algae. Our preliminary results indicate that the inner membrane can be divided in the absence of outer membrane dynamics in yeast. We plan to employ a combination of genome-wide genetic screens and light and electron microscopy to identify the components that are involved in this process. Furthermore, we propose to use a novel high throughput electron microscopy screen to systematically identify genes that are required for mitochondrial ultrastructure maintenance. We are confident that the planned experiments will substantially contribute to our understanding of the mechanisms that determine the morphology and dynamics of the mitochondrial inner membrane.
Selected Review
Klecker, T., and Westermann, B. (2021). Pathways shaping the mitochondrial inner membrane. Open Biol. 11:210238.
https://doi.org/10.1098/rsob.210238