Highly Specialized Mechanisms for Mitochondrial Transport in Neurons: From Intracellular Mobility to Intercellular Transfer of Mitochondria

Abstract

The highly specialized structure and function of neurons depend on a sophisticated organization of the cytoskeleton, which supports a similarly sophisticated system to traffic organelles and cargo vesicles. Mitochondria sustain crucial functions by providing energy and buffering calcium where it is needed. Accordingly, the distribution of mitochondria is not even in neurons and is regulated by a dynamic balance between active transport and stable docking events. This system is finely tuned to respond to changes in environmental conditions and neuronal activity. In this review, we summarize the mechanisms by which mitochondria are selectively transported in different compartments, taking into account the structure of the cytoskeleton, the molecular motors and the metabolism of neurons. Remarkably, the motor proteins driving the mitochondrial transport in axons have been shown to also mediate their transfer between cells. This so-named intercellular transport of mitochondria is opening new exciting perspectives in the treatment of multiple diseases.

Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome c Oxidase: Implications for Brain Bioenergetics

“…Identification of mitochondrial motor-adaptor transport complexes KIF5-Milton-Miro [123][124][125][126], KIF5-syntabulin [127], and SNPH-DYNLL1 anchoring to cytoskeleton [128], with Miro serving as a calcium sensor that controls mitochondrial movement [123,124,129], provide molecular targets for such regulation. These mechanisms enable neurons to maintain proper densities of stationary mitochondria within axons and near synapses (see review [130]).…”