Functions and dysfunctions of mitochondrial dynamics
Scott A. Detmer and David C. Chan
Abstract | Recent findings have sparked renewed appreciation for the remarkably dynamic nature of mitochondria. These organelles constantly fuse and divide, and are actively transported to specific subcellular locations. These dynamic processes are essential for mammalian development, and defectslead to neurodegenerative disease. But what are the molecular mechanisms that control mitochondrial dynamics, and why are they important for mitochondrial function? We review these issues and explore how defects in mitochondrial dynamics might cause neuronal disease.
Invaginations of the mitochondrial inner membrane.
A cytosolic structure, found in some insect spermatids, that is formed by the fusion of mitochondria.
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA. Correspondence to D.C.C. e-mail: firstname.lastname@example.org doi:10.1038/nrm2275 Published online 10 October 2007
In the 1950s, seminal electron microscopy studies led to the canonical view of mitochondria as bean-shaped organelles. These studiesrevealed the ultrastructural hallmarks of mitochondria, which include double lipid membranes and unusual inner membrane folds termed cristae . Recent studies have led to renewed appreciation for the fact that the mitochondrial structure is highly dynamic1,2. Mitochondria have drastically different morphologies depending on the cell type and, even in the same cell, mitochondria can take on a range ofmorphologies, from small spheres or short rods to long tubules. In fibroblasts, for example, mitochondria visualized with fluorescent proteins or specific dyes typically form tubules with diameters of ~0.5 mm, but their lengths can range from 1–10 mm or more. Even more remarkably, imaging studies in live cells indicate that mitochondria constantly move and undergo structural transitions.Mitochondrial tubules move with their long axes aligned along cytoskeletal tracks3. Individual mitochondria can encounter each other during these movements and undergo fusion, resulting in the merging of the double membranes and the mixing of both lipid membranes and intramitochondrial content (BOX 1). Conversely, an individual mitochondrion can divide by fission to yield two or more shorter mitochondria.What are the molecular mechanisms that underlie these unusual behaviours, and do they have consequences for mitochondrial function and cell physiology? In this Review, we discuss the dynamic nature of mitochondria and summarize the mechanisms that drive mitochondrial fusion and fission. In addition, we discuss recent insights into how these processes affect the function of mitochondria. As well ascontrolling the
shape of mitochondria, fusion and fission are crucial for maintaining the functional properties of the mitochondrial population, including its respiratory capacity. Moreover, mitochondrial dynamics has key roles in mammalian development, several neurodegenerative diseases and apoptosis.
Mitochondria as dynamic organelles By several criteria, mitochondria are dynamic organelles.First, the shape and size of mitochondria are highly variable and are controlled by fusion and fission. Second, mitochondria are actively transported in cells and they can have defined subcellular distributions. Finally, the internal structure of mitochondria can change in response to their physiological state.
Dynamic shape. The length, shape, size and number of mitochondria are controlled byfusion and fission (FIG. 1a). At steady state, the frequencies of fusion and fission events are balanced 4 to maintain the overall morphology of the mitochondrial population. When this balance is experimentally perturbed, dramatic transitions in mitochondrial shape can occur. Genetic studies in yeast and mammals indicate that cells with a high fusion-to-fission ratio have few mitochondria, and...