QBI presents a seminar with Ewa Bomba-Warczak, a tenure track Assistant Professor in the Department of Physiology at the University of Pennsylvania Perelman School of Medicine.

Dr. Bomba-Warczak's research investigates how cells with exceptionally long lifespans – neurons and oocytes - establish and maintain their mitochondrial networks throughout their life, and how the stability of mitochondrial components contributes to cell’s health and age-dependent degeneration. In her laboratory she combines in vitro cell and in vivo mouse models with mass spectrometry-based proteomics, biochemistry, genetics, and fluorescent imaging to define the mechanisms governing the lifelong mitochondrial homeostasis in health and disease. 

Dr. Bomba-Warczak received her PhD in Neuroscience from the University of Wisconsin – Madison in 2017 in the laboratory of Dr. Edwin Chapman, and HHMI Investigator, followed by postdoctoral studies under the mentorship of Dr. Jeffrey Savas at Northwestern University. She received her B.S. in Biological Sciences with honors from University of Illinois at Chicago. She is a recipient of a Jerzy Rose Award for most outstanding graduate thesis in Neuroscience at the University of Wisconsin-Madison, NIH F32 Fellowship and NIH MOSAIC K99 Pathway to Independence Fellowship to Promote Diversity. She has been named a Leading Edge Fellow (class of 2023) and recently a Keystone Fellow (class of 2025). She is also a co-founder of MITOchats, an online seminar series featuring graduate students and postdoctoral fellows working in the field of mitochondria. 

Talk Title: Mitochondrial Long-lived Proteins - What Are They and Why Do They Exist? 

Continuous replenishment of mitochondria is essential for maintaining high-quality organelles throughout the lifespan of post-mitotic and long-lived cells. Age-related impairments in mitochondrial renewal contribute to progressive cellular and tissue degeneration. Accordingly, the average half-life of mitochondrial proteins in the mammalian brain is estimated at less than 3 weeks. However, we found that a discrete subset of the mitochondrial proteome persists for months in mammalian brains, hearts, and oocytes, without being turned over. These mitochondrial long-lived proteins, or mt-LLPs, are enriched at cristae invaginations and include OxPhos, MICOS, mt-DNA proteins, chaperones, and cytochrome C.

Dr. Bomba-Warczak's group performed cross-linking MS-based quantitative analysis on native OxPhos complexes which revealed a significant spatial restriction of mt-LLPS and co-preservation within same cristae. Since cristae stability is intimately coupled to mitochondrial function, they propose that mt-LLPs could play a previously unrecognized role in the long-term stabilization of mitochondrial ultrastructure, which in turn might be imperative for mitochondrial fitness. Their ongoing research efforts are centered on (1) the investigation of molecular quality-control mechanisms governing the exceptional persistence of mt-LLPs, (2) the spatio-temporal distribution of mt-LLP within mitochondrial networks in two types of long-lived cells: neurons and oocytes, and (3) their persistence in the context of cristae stability and remodeling. Insights from this work will provide with a new understanding of the role of long-lived proteins in post-mitotic and long-lived cells and could lead to novel targets for potential therapeutic interventions for both neurological disorders and reproductive health. 

Hosted by Nevan Krogan