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

Abstract

Mitochondria and intermediate filament (IF) accumulations often occur during imbalanced axonal transport leading to various types of neurological 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. Depletion of IFB-1 leads to mild dye-filling and significant chemotaxis defects as well as reduced life span. Sensory neuron development is affected and mitochondria transport is slowed down leading to reduced densities of these organelles. Mitochondria tend to cluster in neurons of IFB-1 mutants likely dependent on fission but independent of fusion events. Oxygen consumption and mitochondrial membrane potential is measurably reduced in worms carrying mutations in the ifb-1 gene. Membrane potential also seems to play a role in transport such as FCCP treatment led to increased directional switching of mitochondria. 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 critical (transient) anchor points for mitochondria during their long-range transport in neurons for steady and balanced transport. Abstract Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/723205v3_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1c6fc73org.highwire.dtl.DTLVardef@e7fd9aorg.highwire.dtl.DTLVardef@ba9742org.highwire.dtl.DTLVardef@20a9ed_HPS_FORMAT_FIGEXP M_FIG C_FIG SynopsisVarious neurological diseases are both associated with abnormal accumulations of neuronal intermediate filaments as well as mitochondria. Here, we report a link between these two phenomena employing the model organisms C. elegans. Depletion of neuronal intermediate filament IFB-1 impairs the transport of mitochondria in sensory neurons leading to clustered and accumulated mitochondria affecting neuronal growth and oxygen consumption in nematodes.