ABSTRACT
Neurodegenerative Diseases ....................................................................... 368 16.5.1 OPA1 Mutations: Autosomal Dominant Optic Atrophy .............. 369 16.5.2 Mfn2 Mutations: CMT Type 2A .................................................. 370 16.5.3 GDAP1 Mutations: CMT Type 4A ............................................... 372 16.5.4 Drp1 Mutations: Abnormal Brain Development .......................... 373 16.5.5 LETM1 mutations: The Wolf-Hirschhorn Syndrome ................. 374
16.6 Abnormal Mitochondrial Dynamics Is Associated to Major Degenerative Disorders ............................................................................... 374 16.6.1 Mitochondria-Endoplasmic Reticulum Communication ............. 375 16.6.2 Mitochondrial Quality Control ..................................................... 376 16.6.3 Impaired Mitochondrial Trafcking ............................................ 376
16.7 Future Prospects ......................................................................................... 377 Acknowledgments .................................................................................................. 378 References .............................................................................................................. 378
Mitochondria were described for the rst time in the mid-1800s as granular cytoplasmic compartments with their own membrane. At the end of the 19th century, these organelles were named mitochondrion, coined from the Greek words mitos and chondros, meaning thread and grain, respectively. Mitochondria were considered as independent and isolated organelles for decades. At the beginning of the 20th century, it was revealed that mitochondria show distinct morphologies, probably because of their dynamic nature (Lewis and Lewis 1914), thanks to advances in bright-eld microscopy and in cell culture. It was not until the late 1960s when the rst functional evidence of mitochondrial fusion events was described on the basis of the demonstration of mitochondrial DNA recombination and complementation in yeast (Thomas and Wilkie 1968). Later on, there were further descriptions of mitochondrial fusion events and mitochondrial network formation also in mammalian cells (Bakeeva et al. 1978, 1981; Kimberg and Loeb 1972). In the 1990s, the development of mitochondria-targeted uorescent dyes and proteins allowed the visualization of mitochondrial dynamics in several cellular models, from yeast to hepatocytes (Bereiter-Hahn and Voth 1994; Cortese et al. 1998; Nunnari et al. 1997). This dynamism refers to the movement of mitochondria along the cytoskeleton and also to mitochondrial shape changes, which are controlled by fusion and ssion events. In 1997, the rst gene that participates in the fusion of mitochondria was discovered in Drosophila melanogaster (Hales and Fuller 1997). In the past decade, several genes that modulate mitochondrial fusion and ssion have been identied, rst in yeast and later in mammalian cells (Yaffe 1999). Although great advances have been achieved in the study of mitochondrial dynamics in recent years, the mechanisms that regulate fusion and ssion processes remain to be elucidated. The physiological relevance of mitochondrial dynamics in mammalian tissues is not well understood, and the factors that determine differences in mitochondrial morphology and dynamics among distinct cell types need to be dened. In this review, we summarize current knowledge of mitochondrial fusion and ssion in mammals and their involvement in mitochondrial metabolism and neurodegeneration.
