Mitochondrial Morphology and Dynamics in Yeast and Multicellular Eukaryotes

Abstract

Mitochondria form dynamic tubular networks that continually change their shape and move throughout the cell. In eukaryotes, these organellar gymnastics are controlled by numerous pathways that preserve proper mitochondrial morphology and function. The best understood of these are the fusion and fission pathways, which rely on conserved GTPases and their binding partners to regulate organelle connectivity and copy number in healthy cells and during apoptosis. In budding yeast, mitochondrial shape is also maintained by proteins acting in the tubulation pathway. Novel proteins and pathways that control mitochondrial dynamics continue to be discovered, indicating that the mechanisms governing this organelle's behavior are more sophisticated than previously appreciated. Here we review recent advances in the field of mitochondrial dynamics and highlight the importance of these pathways to human health.

Mitochondria and cancer: is there a morphological connection?

“…In the past years, a number of groups showed that mitochondria are dynamic structures that undergo fusion and fission events continuously throughout the life of a cell (Okamoto and Shaw, 2005). Mounting evidence indicate that mitochondrial dynamics have roles beyond maintenance of morphology, and impact on both cell death and cell metabolism .…”

“…It is thought to recruit Drp1 to punctuate structures on mitochondria and is thus considered as the limiting factor in the fission process (Stojanovski et al, 2004). The mechanism of constriction is not understood but the current model postulates that Drp1 homooligomerizes and forms a ring around the mitochondrial tubule (Okamoto and Shaw, 2005). Drp1 complexes might generate mechanical force via conformational changes, leading to membrane constriction, similar to dynamin (Danino et al, 2004).…”

Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis

“…The protein machinery that regulates mitochondrial fission and fusion has been well characterized and reviewed in detail. 8 In mammalian cells, at least two proteins, dynamin-related protein 1 (Drp1) and hFis1, are required for mitochondrial fission. 9,10 Drp1 is a large GTPase that translocates to puncta on mitochondria, where it couples GTP hydrolysis with mitochondrial membrane constriction and fission.…”

Dynamique et morphologie mitochondriales

“…Les premiers tests de fusion mitochondriale, in vivo et in vitro, ont été réalisés chez S. cerevisiae [2,4]. Cette levure existe sous deux formes haploïdes capables de se conjuguer.…”

“…Le développement de nouvelles techniques de microscopie (microscopie électronique à tomographie, microscopie confocale) vers la fin du XX e siècle révéla à nouveau que les mitochondries peuvent adopter une structure punctiforme ou tubulaire. Dans les années 1990, des cribles génétiques menés chez la levure Saccharomyces cerevisiae ont conduit à l'isolement de mutants dont la morphologie des mitochondries était altérée et à l'identification des premières protéines impliquées dans la dynamique mitochondriale [2]. S. cerevisiae présente un réseau mitochondrial filamenteux qui résulte d'un équilibre dynamique entre deux forces antagonistes de fission et de fusion ( Figure 1A, B).…”