Methods To Interrogate Mitochondrial Biology In Health And Disease

TOPICAL COLLECTIONS

Guest Editors

Tslil Ast

Massachusetts General Hospital and the Broad Institute of MIT and Harvard

Tslil Ast, PhD, is a postdoctoral associate at the lab of Prof. Vamsi K Mootha jointly based at Massachusetts General Hospital and the Broad Institute of MIT and Harvard. Her research focuses on iron-sulfur (Fe-S) cluster generation in human health and disease. To this end, she applies genetic, biochemical, and cell biological tools to better understand this essential pathway and its interplay with other processes. She found that a key mitochondrial factor in Fe-S cluster biogenesis, FXN, whose loss is linked to the most common inherited ataxia, can be made redundant in hypoxia. Current work is focused on building on this finding to generate a safe and practical therapeutic approach for patients. This postdoctoral work was supported by EMBO and the Helen Hay Whitney Foundation and earned her the 2021 ESL scientific excellence award. Previously, she earned her PhD from the Weizmann Institute of Science, studying protein import into the endoplasmic reticulum with Prof. Maya Schuldiner.

Raz Bar-Ziv

University of California, Berkeley

Dr. Raz Bar-Ziv (https://www.razbarziv.com/) is a postdoctoral fellow with Professor Andrew Dillin at the University of California, Berkeley, in the Immunology and Molecular Medicine division of the Molecular and Cell Biology department (https://www.dillinlab-berkeley.org). Dr. Bar-Ziv obtained his PhD in 2017 by studying the regulation of dynamics of gene expression and chromatin during DNA replication, by developing, applying, and analyzing high-throughput sequencing data, under the mentorship of Professor Naama Barkai at the Weizmann Institute of Science in Israel. For his postdoctoral studies, Dr. Bar-Ziv is studying the mechanisms responsible for the failure of protein homeostasis during aging in different tissues, with a particular interest in mitochondrial protein homeostasis. Dr. Bar-Ziv focuses on revealing the mechanisms by which neurons and glia communicate mitochondrial regulation within the nervous system, and to peripheral tissues. He found that astrocyte-like glial cells are cellular regulators of mitochondrial protein homeostasis, able to modulate mitochondrial proteostasis in neurons. Dr. Bar-Ziv is interested in answering questions relating to tissue communication in the context of neurodegeneration and aging. He won multiple awards throughout his career for scientific excellence and has been supported by postdoctoral fellowships funded by The Larry L. Hillblom Foundation and the European Molecular Biology Organization. In addition to his scientific work, Dr. Bar-Ziv volunteers in a non-profit organization, ScienceAbroad, where he is the field manager for Genetics and Cell Biology, and as an associate in the American Society of Cell Biology (ASCB) LGBTQ+ Committee.

Collection Overview

The mitochondrion is a key organelle, functioning as a biosynthetic, bioenergetic, and signaling hub in the eukaryotic cell. This organelle must coordinate many crucial cellular functions, with more being discovered every decade, including ATP generation via oxidative phosphorylation, catabolism of fatty acids, assembly of iron-sulfur clusters, amino acid and vitamin metabolism, hormone synthesis, and cell death. Importantly, mitochondrial dysfunction is one of the hallmarks of aging and has also been tightly linked to many rare and common diseases.

Our ability to understand mitochondrial biology in health and disease states is governed by our ability to assay and quantify the many different functions and pathways that mitochondria carry out. Recent advances in organelle-localized sequencing methods, bio-sensor development, genetic editing of genomes, protein and RNA proximity labeling, and imaging techniques have opened a new horizon to study the composition, structure, regulation, and dynamics of mitochondrial components across states.

The goals of the methods in this collection are: (1) to provide detailed protocols of state-of-the-art methods to interrogate key aspects of mitochondrial biology across different experimental systems, including methods harnessing genetic approaches, microscopy-based methods, sequencing-based, and biochemical approaches to measure mitochondrial components, activity, or morphology. (2) to introduce novel approaches, such as biological sensors and tagging approaches, that enable measuring any of the variety of functions localized to mitochondria or in interface with mitochondria.