Loss of intermediate filament IFB-1 reduces mobility, density and physiological function of mitochondria in C. elegans sensory neurons

Abstract

Mitochondria and intermediate filaments (IF) accumulations often occur duringimbalanced axonal transport leading to various types of neurodegenerative diseases. It is still poorly understood whether a link between neuronal IFs and mitochondrial mobility exist. In C. elegans, among the 11 cytoplasmic IF family proteins, IFB-1 is of particular interest as it is expressed in a subset of sensory neurons and forms an obligate heteropolymer with one of the essential IFA proteins critical for worm viability. Depletion of IFB-1 leads to dye-filling and chemotaxis defects as well as reduced life span. Axons grew shorter during development and mitochondria transport is slowed down leading to reduced densities of these organelles in neurons. Oxygen consumption and mitochondrial membrane potential is measurably reduced in worms carrying mutations in the ifb-1 gene. Membrane potential also seemed to play a role in transport such as after FCCP treatment increased directional switching of mitochondria are observed. Mitochondria colocalize with IFB-1 in worm neurons and appear in a complex with IFB-1 in pull-down assays. In summary, we propose a model in which neuronal intermediate filaments may serve as transient anchor points for mitochondria during their microtubule-based long-range transport in neurons.