© 2018. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2018) 221, jeb170027. doi:10.1242/jeb.170027 OUTSIDE JEB Mitochondria are too hot Because of the controversial nature of their Sick ants save findings, Crétien and his colleagues to handle! decided to use various chemicals to impair themselves by acid- mitochondrial function, while monitoring spraying their sisters heat generation using the same fluorescent dye, in order to ensure that their results were real and not due to a faulty organelle or artifacts caused by the dye. To eliminate the possibility that the changes in MTY fluorescence were due to changes in pH and membrane potential of the mitochondria during respiration, the authors treated the human kidney cells with cyanide, oligomycin or respiratory enzyme inhibitors such as rotenone and antimycin MITOCHONDRIA – which are known to affect the mitochondria by altering membrane SICKNESS BEHAVIOUR Back in 1957, in his article published in potential, changing the mitochondrial pH, Scientific American (volume 197, disrupting membrane structure and Nurseries are notorious hotbeds of disease pp. 131–144), biologist Philip Siekevitz affecting the function of the mitochondrial and contagion. Place one snotty child in a called the mitochondrion the ‘powerhouse respiratory enzymes. Indeed, the authors room with 10 healthy kids and you’re on of the cell’, a term very much used today found that MTY fluorescence correlated the cusp of an epidemic. Now imagine this when we talk about this complex with mitochondrial respiration and that it nursery multiplied by hundreds and you’ll organelle. Mitochondria are organelles that was not due to faulty mitochondria or have an idea of life inside an ant colony, use oxygen and nutrients to generate artifacts in the fluorescence. The where sick ants can easily transmit energy and heat to maintain a stable body researchers further validated their findings pathogens to their sisters. To reduce this temperature. But did you ever wonder how when the response of the dye was enhanced risk, ants use different strategies to detect hot they actually get when they ‘work’ to in the presence of proteins involved in heat and disinfect diseased nestmates, heat us up? A group of researchers did, and generation. Therefore, MTY seems to effectively acting as nurses, executioners their findings are extraordinary: work, and work well, when it comes to or morticians. But what if the nurse mitochondria can heat up to close to 50°C, monitoring mitochondrial heat generation herself is infected? Will she fall victim to even though our core temperature is closely and mitochondria really do seem to run hot disease or can she act to reduce her risks of maintained at 37.5°C. when they are generating energy. further decline? The answer, as shown in an exciting new paper in PNAS by Dominique Crétien, a researcher working Through their work, Crétien and his Matthias Konrad and his colleagues from with Pierre Rustin at the Université Paris 7 the Institute of Science and Technology in in France, along with a team of colleagues have raised even more questions about heat regulation in vertebrates. How Austria, is that it depends on what her international researchers, decided to patient is infected with. investigate how hot mitochondria actually can the mitochondrial enzymes perform so get when they generate heat in healthy efficiently at such high temperatures? What human cells. To do so, the authors used a implications do these findings have for Konrad and his colleagues began by brand-new dye that targets the mitochondrial structure and function? How exposing ants to one of two different mitochondria and changes its do they affect (if at all) how we approach fungal pathogens. The first, called fluorescence with temperature, called mitochondrial disorders and how we treat Metarhizium, kills ants rapidly, while the them? One thing is certain, though: the Beauveria MTY. When the researchers monitored ‘ ’ second, called , causes only the fluorescence of the dye during cellular term powerhouse just got a whole new minimal mortality. When ants infected respiration in a human kidney cell line, meaning. with one pathogen were subsequently they found that mitochondria are able to 10.1242/jeb.170027 co-infected with the other, known as a function at temperatures that are heterologous infection, things got much approximately 10°C higher than the core Crétien, D., Bénit, P., Ha, H.-H., Keipert, S., worse and mortality rates shot up. This, in El-Khoury, R., Chang, Y.-T., Jastroch, M., Jacob, body temperature. The group recorded H. T., Rustin, P. and Rak, M. (2018). Mitochondria itself, is not surprising. Co-infection often this result multiple times and determined are physiologically maintained at close to 50°C. elevates mortality because it forces that, as long as the mitochondria are PLOS Biology 16, e2003992. animals to simultaneously solve distinct functional and have optimal conditions, Oana Birceanu immunological problems. But what was they indeed increase their temperature Wilfrid Laurier University surprising is that the singly infected ants during normal functioning. [email protected] behaved as if they were aware of the added Outside JEB reports on the most exciting developments in experimental biology. The articles are written by a team of active research scientists highlighting the papers that JEB readers can’t afford to miss. Journal of Experimental Biology 1 OUTSIDE JEB Journal of Experimental Biology (2018) 221, jeb170027. doi:10.1242/jeb.170027 dangers of a heterologous infection – and Birds and mammals expressed genes in the mesopallium – a acted to reduce it. region of the brain involved in higher- share smartly designed order processing. Briscoe found a To examine the possibility that singly neurons whopping 78 genes that were uniquely infected ants are risk adverse, the team and highly expressed in the mesopallium. confronted them with a nestmate carrying The team then focused on five of the more the other pathogen. What they found was highly expressed unique genes and both amusing and sensible. In short, singly mapped out their expression visually to infected ants are cranky, just like any other gain a bird’s eye view of how well it sick animal. In contrast to their relatively distinguished the mesopallium from docile uninfected counterparts, singly surrounding brain areas. The stained infected ants bite, grab and drag their brains revealed that the top five genes nestmates about. Worse still, they spray their cleanly delineated the mesopallium from infected nestmates with an antimicrobial other surrounding brain regions, poison, especially if their nestmates carry suggesting the genes are important heterologous infections. Both types of genetic markers for the special cell types response are sophisticated and effective. NEURON ARCHITECTURE that comprise mesopallium. Konrad and his team argue that becoming Birds can do most things just as well as One caveat is that chickens are lower in ornery is part of a suite of adaptive mammals. Crows use tools to solve the cognitive pecking order compared to responses called ‘sickness behaviors’ that complex puzzles. Lyrebirds are expert the linguistic abilities of vocal learning involve things like crankiness, lethargy vocal mimics, putting polyglots to shame. avians, such as songbirds. As a follow-up, and a diminished appetite. By reducing And even the humble pigeon is a the team confirmed that expression of the activity and keeping others at bay, discerning enough art critique to same genes delineated mesopallium in the ‘sickness behaviors’ are thought to help distinguish between paintings by Picasso European starling, a songbird with an animals fight infection. At the same time, and Monet. Nevertheless, birds still get a extensive vocal repertoire, suggesting acid spraying serves two crucial functions. bad rap. Calling someone a ‘bird brain’ these genes are conserved across birds. First, ants that spray have fewer fungal insults their intelligence due in part to bird spores transmitted to them. This lowers brains not having the fanciful folds and While the avian mesopallium and their risk of heterologous co-infection more layers found in mammal brains. mammalian cortex originate from the than twofold, thereby forestalling a same brain region early in life premature death. Second, because sprayed The neocortex, the outer layer of (telencephalon), they take on different ants are disinfected, they become less mammalian brains, is often touted as shapes across development: the cortex dangerous to the rest of the colony. being the hallmark of a mammal’s becomes layered in mammals, whereas advanced cognition. It’s the largest part of clusters of neurons assemble in birds People have a natural aversion to sickness. human brains, and is thought to give rise (referred to as ‘nuclei’). Therefore, Watch the horror in passengers’ eyes when to primates’ advanced intellectual Briscoe and colleagues examined whether someone sneezes on the subway without abilities. As bird brains are smooth and mouse cortex expressed a similar genetic covering their nose and mouth! But we are without layers, it was long presumed signature to that which characterized the generally don’t distinguish between they were behind the times and that their mesopallium. Lo and behold, expression specifictypes of contagion, simply because neurons didn’t play a similar function or of the same five genes that distinguished we don’t know which of the myriad of come from a similar evolutionary origin to the mesopallium outlined the mouse diseases our fellow travelers are carrying. mammals. cortex as well, suggesting the neurons are Did the sneeze indicate flu, the common cut from the same evolutionary cloth. cold or something as benign as a snuffle of However, scientists have begun to peck dust? We can’t tell. But remarkably, away at this ancient notion of ‘bird brain’ The research is fascinating as it suggests infected ants can tell, and moreover they being an insult. In a recent paper that birds and possibly primates evolved then use this recognition to dictate their published in Current Biology, Steven intelligence independently and that behavior.