Mitochondria are fascinating eukaryotic organelles that have allured microscopists for centuries. Their exquisite embodiment of the “form follows function” paradigm renders mitochondria an ideal specimen for investigation with a variety of imaging modalities—ranging from Palade’s electron micrographs exposing their inner membrane labyrinth to time-lapse fluorescence movies tracking their shape-shifting behaviors.
Although commonly referred to as “Powerhouses of the Cell” for their role in metabolism and ATP generation, mitochondria are also expert “Stress Sensors of the Cell”, reflecting their contribution as a central hub for integrating several cell stress pathways. Interestingly, mitochondrial networks undergo dramatic morphological remodeling in response to varying stress conditions, and in this manner, mitochondrial shape can be used as a readout for overall cellular health. In fact, a hallmark feature of many neurodegenerative diseases is the presence of mitochondria with severely altered morphologies that reflect their impaired function. Although the link between altered mitochondria and disease pathology is well established, the cellular mechanisms that facilitate mitochondrial shape changes that lead to organellar and cellular dysfunction remain poorly defined.
In the Grotjahn Lab, we are interested in studying the functional and structural interactions that mediate these stress-induced modulations to mitochondrial networks using techniques that directly bridge the intersection between cellular, molecular and structural biology fields, including whole-cell cryo-electron tomography (cryo-ET), cryo-focused ion beam (cryo-FIB) milling, and correlative light and electron microscopy (CLEM). Through our high-resolution cellular imaging efforts, we shine new light the physiological and pathogenic mechanisms that contribute to mitochondrial dysfunction and disease.