Mitochondrial dynamics in health and disease

Our laboratory investigates the central mechanisms that regulate mitochondrial function—including fusion–fission dynamics, degradation pathways, interactions with other organelles, and protein homeostasis. We study how these processes impact cellular physiology, development, and human disease. Because neurons are particularly reliant on mitochondrial integrity, our research provides insight into the mechanisms underlying neurodegenerative disorders and potential therapeutic strategies.

Introduction to mitochondria

Mitochondria are essential organelles that serve as the primary power generators of eukaryotic cells, producing ATP through oxidative phosphorylation (OXPHOS). Beyond energy production, mitochondria host the tricarboxylic acid (TCA) cycle, fatty acid oxidation, and numerous other metabolic pathways. They also perform diverse roles in apoptosis, calcium signaling, reactive oxygen species (ROS) production, innate immunity, phospholipid synthesis, and iron–sulfur cluster biogenesis. Because of their central importance to cellular function, mitochondrial dysfunction contributes to a wide range of human diseases, particularly those affecting the nervous, cardiovascular, and muscular systems.

Highly unusual organelles

Mitochondria are believed to have originated from an ancient endosymbiotic event in which a free-living prokaryote merged with an ancestral eukaryotic cell. Along with this unusual evolutionary origin, mitochondria have several distinctive features compared to other cellular organelles.

First, mitochondria are enclosed by a double membrane that defines multiple compartments: the outer mitochondrial membrane, the intermembrane space, the inner mitochondrial membrane, and the matrix (the innermost compartment). The inner membrane is extensively folded into involuted structures known as cristae, which increase the surface area available for energy-generating reactions.

Second, mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is circular and encodes 13 proteins, 22 tRNAs, and 2 rRNAs. The tRNAs and rRNAs form part of the mitochondrial translation machinery, while the 13 protein-coding genes encode essential subunits of the oxidative phosphorylation (OXPHOS) system. Although mitochondria possess their own genome, most of the mitochondrial proteome—comprising roughly 1,000–1,500 proteins—is encoded by nuclear genes and imported into the organelle after synthesis in the cytosol. Of note, OXPHOS holoenzymes in the mitochondrial inner membrane are composed of proteins encoded by both the nuclear and mitochondrial genomes, making mitochondria reliant on tight coordination of gene expression between the two genetic systems.

Finally, mitochondria in humans are inherited exclusively from the mother. As a result, diseases caused by mutations in mtDNA follow a maternal inheritance pattern, in contrast to Mendelian diseases (including some mitochondrial disorders) arising from mutations in nuclear genes.

Mitochondrial dynamics

More than a century ago, cell biologists discovered that mitochondria in living cells exhibit strikingly dynamic behaviors. Each cell contains dozens to hundreds of mitochondria, which can be visualized using fluorescent or vital dyes that accumulate within them. Early live-cell imaging revealed that mitochondria frequently collide and fuse, forming interconnected networks, and then divide again into separate organelles. These observations established that mitochondria exist not as static entities but as a dynamic population that continually undergoes cycles of fusion and fission.
In addition to these shape- and identify-changing events, mitochondria move throughout the cytoplasm along cytoskeletal tracks composed of actin filaments and microtubules. This motility enables mitochondria to distribute within the cell according to metabolic needs and signaling demands.

The term mitochondrial dynamics encompasses this ongoing fusion, fission, and transport. Together, these processes determine the morphology, number, size, and spatial distribution of mitochondria—and, most importantly, regulate their physiological function. Through these dynamic behaviors, mitochondria integrate their structure with their role in energy production, signaling, and cell health.