Mitochondrial Dynamics in Mitochondrial Diseases

Abstract

Mitochondria are very versatile organelles in continuous fusion and fission processes in response to various cellular signals. Mitochondrial dynamics, including mitochondrial fission/fusion, movements and turnover, are essential for the mitochondrial network quality control. Alterations in mitochondrial dynamics can cause neuropathies such as Charcot-Marie-Tooth disease in which mitochondrial fusion and transport are impaired, or dominant optic atrophy which is caused by a reduced mitochondrial fusion. On the other hand, mitochondrial dysfunction in primary mitochondrial diseases promotes reactive oxygen species production that impairs its own function and dynamics, causing a continuous vicious cycle that aggravates the pathological phenotype. Mitochondrial dynamics provides a new way to understand the pathophysiology of mitochondrial disorders and other diseases related to mitochondria dysfunction such as diabetes, heart failure, or Hungtinton's disease. The knowledge about mitochondrial dynamics also offers new therapeutics targets in mitochondrial diseases.

Keywords: mitochondrial disease; mitochondrial dynamics; mitochondrial fusion; mitocondrial fission; mitophagy.

Figure 1

Scheme showing the main proteins implicated in mitochondrial dynamics. MOM: Mitochondrial outer membrane; MIM: Mitochondrial inner membrane.

Figure 2

Scheme illustrating the role of mitochondrial dynamics in mitochondrial diseases. Mitochondrial dysfunction and reactive oxygen species (ROS) production induces decreased mitochondrial fusion and mitochondrial fragmentation and mitophagy. Elimination of dysfunctional mitochondria, associated to increased mitochondrial biogenesis, restores ATP levels, decreases ROS production and increases mitochondrial fusion and function.