Kojima, W. | Search bioRxiv

bioRxiv2023

Optineurin provides a mitophagy contact site for TBK1 activation

Tank-binding kinase 1 (TBK1) is a Ser/Thr kinase involved in many intracellular processes including innate immunity, cell cycle, and apoptosis. TBK1 is also important for phosphorylating autophagy adaptors critical in selective autophagic removal of damaged mitochondria (mitophagy). However, the mechanism by which TBK1 is activated by PINK1/Parkin-mediated mitophagy remains largely unknown. Here, we show that the autophagy adaptor OPTN provides a unique platform for TBK1 activation. The OPTN-ubiquitin and OPTN-autophagy machinery interaction axes facilitate assembly of the OPTN-TBK1 complex at a contact site between damaged mitochondria and the autophagosome formation site. This assembly point serves as a positive feedback loop for TBK1 activation by accelerating hetero-autophosphorylation of the protein. Furthermore, expression of monobodies engineered in this study against OPTN impaired assembly of OPTN at the contact sites as well as the subsequent activation of TBK1 and mitochondrial degradation. Taken together the findings reveal that a positive reciprocal relationship between OPTN and TBK1 initiates autophagosome biogenesis on damaged mitochondria.

cell biology↗

bioRxiv2023

Evolution of horn length and lifting strength in the Japanese rhinoceros beetle Trypoxylus dichotomus

Rhinoceros beetle (Trypoxylus dichotomus) males have pitchfork-shaped head horns, which they use to pry rival males from the trunks of trees. In the largest males these horns can be three times the length of horns in the two closest sister species. Because this weapon functions as a lever, longer horns should lift with less force than shorter horns (the paradox of the weakening combatant) unless other elements of the weapon system (e.g., input lever length, muscle mass) evolve to compensate. We used next-generation sequencing approaches to consolidate 23 sample locations into 8 genetically distinguishable populations, reconstructing their historical relationships and providing a comprehensive picture of the evolution of this horn lever system. We show that head horns likely increased in length independently in the Northern and Southern lineages. In both instances this resulted in weaker lifting forces, but this mechanical disadvantage was later ameliorated, to some extent and in some locations, by subsequent reductions to horn length, changes in muscle size, or by an increase in input lever length (head height). Our results reveal an exciting geographic mosaic of differences in weapon size, weapon force, and in the extent and nature of mechanical compensation. Reconstructing the evolution of this weapon system offers critical insights towards meaningfully linking mating system dynamics, selection patterns, and diversity in sexually selected traits.

evolutionary biology↗