Research Description:

Lifelong maintenance of mitochondrial networks in long-lived cells

Mitochondria have a remarkable ability to tailor their morphology, function, and behavior according to the specialized needs of the cell they inhabit. These differences translate to functional and behavioral specializations, which are critical for cells to fulfill their dedicated functions. For example, in highly polarized neurons, mitochondrial morphology differs dramatically from an interconnected network in the soma, to parallel arrays within dendritic arbors, and shorter organelle units along axons. Despite understanding many of the players involved in mitochondrial dynamics and turnover, little is known about how these distinct mitochondrial networks are built and sustained. To achieve this, cells must synchronize multiple pathways including multilevel quality-control, coordination of mito-nuclear gene expression, and network replenishment following degradation. Our research group is interested in defining how cells, particularly neurons and oocytes, establish their diverse mitochondrial populations and maintain their health throughout the cells’ lifetime.

Our lab’s main research areas center on:

1. kinetics of mitochondrial biogenesis from the DNA to proteins to intact organelles
2. mitochondrial proteome and genome turnover and replenishment along the development and aging continuum
3. molecular and environmental determinants of mitochondrial specialization

Our laboratory employs cutting-edge technologies encompassing mass spectrometry-based proteomics and metabolomics, biochemistry, cell biology, metabolic labelling and tracing, cross-linking MS and structural biology – in both in vitro and in vivo mouse models – to investigate lifelong fidelity of mitochondrial proteome and genome in healthy and diseased mammalian systems.