Project Details
Projekt
Contributions of ubiquitin signaling to the maintenance of mitochondrial import channels
Subject Area
Cell Biology
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 541727789
This project focuses on understanding the role of ubiquitin signaling in maintaining the quality of mitochondria, the cellular powerhouses responsible for energy production and metabolic processes. To function effectively, mitochondria rely on a well-orchestrated protein import process through the translocase of the outer mitochondrial membrane (TOM) complex. When TOM proteins become faulty, mitochondria use specialized structures called mitochondria-derived vesicles (MDVs) to remove and discard these damaged components, thereby preserving mitochondrial health and functionality. The project has three main aims: 1) Defining the Ubiquitylation Response: We hypothesize that blocking the TOM complex will trigger MDV formation through ubiquitin-regulated processes. We will use genetic approaches to induce TOM complex blockage and then study the resulting changes in protein ubiquitylation using targeted and unbiased methods. 2) Evaluating the Mechanism of Ubiquitylation: To understand the functional significance of ubiquitylation in response to TOM complex blockage, we will investigate how specific ubiquitylation targets affect MDV formation. This will involve mutagenesis to eliminate specific ubiquitin modifications and the use of tools to manipulate the ubiquitylation status of target proteins. 3) Assessing Consequences on Mitochondrial Function: Here, we will examine how altering key ubiquitylation events impacts cellular and mitochondrial function and morphology in response to defects in protein import. This will provide insight into the physiological implications of ubiquitin signaling in maintaining mitochondrial proteostasis. In summary, this project seeks to unravel the "ubiquitin code" governing the quality control pathway for mitochondrial import channels, shedding light on how ubiquitin signaling influences mitochondrial health, function, and shape. Understanding these mechanisms could have broader implications for cellular health and metabolism.
DFG Programme
Priority Programmes
