The Journal of Membrane Biology

, Volume 252, Issue 4–5, pp 293–306 | Cite as

A Molecular Perspective on Mitochondrial Membrane Fusion: From the Key Players to Oligomerization and Tethering of Mitofusin

  • Dario De VecchisEmail author
  • Astrid Brandner
  • Marc Baaden
  • Mickael M. Cohen
  • Antoine TalyEmail author
Part of the following topical collections:
  1. Membrane and Receptor Dynamics


Mitochondria are dynamic organelles characterized by an ultrastructural organization which is essential in maintaining their quality control and ensuring functional efficiency. The complex mitochondrial network is the result of the two ongoing forces of fusion and fission of inner and outer membranes. Understanding the functional details of mitochondrial dynamics is physiologically relevant as perturbations of this delicate equilibrium have critical consequences and involved in several neurological disorders. Molecular actors involved in this process are large GTPases from the dynamin-related protein family. They catalyze nucleotide-dependent membrane remodeling and are widely conserved from bacteria to higher eukaryotes. Although structural characterization of different family members has contributed in understanding molecular mechanisms of mitochondrial dynamics in more detail, the complete structure of some members as well as the precise assembly of functional oligomers remains largely unknown. As increasing structural data become available, the domain modularity across the dynamin superfamily emerged as a foundation for transfering the knowledge towards less characterized members. In this review, we will first provide an overview of the main actors involved in mitochondrial dynamics. We then discuss recent example of computational methodologies for the study of mitofusin oligomers, and present how the usage of integrative modeling in conjunction with biochemical data can be an asset in progressing the still challenging field of membrane dynamics.


Mitofusin Fzo1 Mitochondrial dynamics Mitochondrial fusion Mitochondrial fission Dynamin-related proteins 



This work was supported by the “Initiative d’Excellence” program from the French State (Grants “DYNAMO,” ANR-11-LABX-0011, and “CACSICE,” ANR-11-EQPX-0008).

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest.

Research Involving Human Participants and/or Animals

This research does not involve human participants or animals.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Medicine, Leeds Institute of Cardiovascular and Metabolic MedicineUniversity of LeedsLeedsUK
  2. 2.CNRS, Université de Paris, UPR 9080Laboratoire de Biochimie ThéoriqueParisFrance
  3. 3.Institut de Biologie Physico-Chimique - Fondation Edmond de RothschildPSL Research UniversityParisFrance
  4. 4.Laboratoire de Biologie Cellulaire et Moléculaire des EucaryotesSorbonne Université, CNRS, UMR 8226ParisFrance

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