Intracellular networking: coupling of mitochondrial energy metabolism with microtubule-dependent mRNA logistics

Eukaryotic cells are particularly characterized by the integration of an endosymbiont, which has gradually led to the development of highly specialized organelles. During the adaptation process, almost the entire genetic material of the endosymbiont was transferred into the nucleus of the host, significantly increasing the complexity of cellular logistics. Consequently, not only complex protein translocation systems had to evolve in the envelope membranes of the organelles, but also intensive bidirectional communication between the organelle and the cell nucleus in order to fine-tune the availability and demand for specific compounds in the organelle and the surrounding cell at any given time.

In the polar-growing fungus Ustilago maydis, which has emerged as a new model system for cell biology, we discovered a novel link between endosomal long-distance transport of mRNA and mitochondrial energy metabolism. The key RNA-binding protein Rrm4 binds numerous nuclear-encoded mitochondrial mRNAs and loss of rrm4 causes defects in the formation of mitochondrial respiratory chain complexes. We used genetic engineering coupled with life-cell imaging to track the distribution of Atp3, the γ subunit of ATP synthase, in polar-growing cells with regulatable Rrm4. Fusion of Atp3 with photoconvertible fluorescent protein (tdEosFP), which can be converted from green to red emission upon exposure to violet light, enabled us to demonstrate that mitochondrial localization of newly synthesized Atp3 is dependent on long-distance transport in polar hyphae. Genome-wide transcript analysis indicates that U. maydis hyphae with defective microtubule dependent long-distance transport undergo a significant metabolic shift, suggesting a compensatory response to impaired mitochondrial function. To assess metabolic changes on a temporal-quantitative scale we are implementing genetically encoded, ratio metric Matryoshka biosensors for ATP and NADH in our life-cell imaging coupled with sophisticated metabolomics.

Overall, we show that in polar cells such as fungal hyphae or neurons, mRNA logistics post-transcriptionally regulate mitochondrial energy metabolism, revealing key insights into host-organelle networking. However, our understanding of the principles underlying the establishment, maintenance and evolution of intracellular microbial associations, such as endosymbiont-derived organelles, remains in its very early stage.