Although mitochondria may appear to be separate entities, they can also intertwine throughout their entire life cycle. For decades, scientists have known that mitochondria fuse together membranes to form single, branching structures. They then cleave back into individual cells by fission. Jodi Nunnari, University of California, Davis' pioneering researcher on these dynamics, stated that both of these processes are constantly changing depending on the state of the cell.These mitochondrial rendezvous have multiple functions, but at least one seems to be cooperative. Fusing with healthy neighboring mitochondria can save single mitochondria without a genome, or those that have one. Nunnari stated that the connected structures provide a means for chemical signals and proteins to be shared, and that fusion may help distribute proteins more evenly among mitochondria. Fusion doesn't necessarily mix all things. She said that it is important to keep a bit of your individuality, even within a network.Are Electromagnetic Signals Possible?It is becoming more clear that mitochondria can interact in other ways than just fusing. They can also shuttle substances through more casual kiss-and-run events, in which they briefly join the membranes or by long protrusions known as nanotunnels. These are common in cells that have less mobility.Picard and his coworkers discovered a new mode of communication while Picard was a postdoc at the Children's Hospital of Philadelphia in 2015. Mammalian cells can create connections at the points where mitochondria touch to align their cristae. These are the dark inner membrane folds which look like grill marks in micrographs. To achieve this kind of alignment, mitochondria must communicate with each other about their cristae positions and then realign them accordingly.Picard stated that he believes there is an electromagnetic signal being transmitted. He suggested that charged ions are being pumped across the membrane by molecules derived from food. This creates a potential of about 180 millivolts. The resulting force of ions rushing across the membrane to equalize this difference is used for the generation of ATP. It also creates an electric current and a magnetic field. It is possible that an electromagnetic signal between mitochondria is being transmitted faster than the chemical signals between organelles. It is not yet clear if this additional speed has any functional significance.Researchers are likely to continue discovering new interactions. Brian ORourke, a Johns Hopkins Medicine cardiac physiologist, stated that we are only beginning to understand how mitochondria communicate with one another.Yet another mystery surrounds the purpose of all this communication. Natalie Porat-Shliom is a cell biologist at National Cancer Institute. She suggests that social behavior improves efficiency of the entire organism. She said that all these responses can be tuned to optimize metabolism and function.The Pros and Cons Of SynchronizationFor example, mitochondrial chatter can synchronize energy production between cells that work together in some cases. Porat-Shliom was studying salivary gland acinar cells, which work together to produce saliva, many years ago. The team observed that salivary gland cells in anesthetized rats had synchronization with their mitochondria. In many cases, these membrane potentials were increasing and decreasing at the same time as the cells weren't secreting.Porat-Shliom believes that mitochondria relay short-lived molecules between each other to couple oscillations among cells. She believes this could coordinate energy bursts to secrete saliva, when all cells are prompted.Similar synchronized oscillations, sometimes called flashes, have been observed in other cell types by other groups. Porat-Shliom said that the phenomenon is not universal. Some cells, like those in the liver don't synchronize their metabolism the same way because they have different functions.ORourke pointed out that synchronization may not be always a good thing. His lab has been studying coupled oscillations between mitochondria that drive the contractions in cardiomyocyte (heart muscle cells) cells for years. He and his colleagues stimulated mitochondria with lasers in small areas of isolated cardiomyocytes. Most of the massive mitochondria began to oscillate together.ORourke views this coupling in terms of a stress response that could have potentially fatal consequences. His team's results show that synchronized activity can sometimes suppress cells contractions, impairing electrical signals transmission from one heart cell to another and disrupting coordinated responses within the heart. They discovered that cardiac arrhythmias can be caused by coupled oscillations when the heart is recovering after an interruption in its blood supply. Pulsed generation of ATP is not possible in the heart like in salivary gland cells. This is because the organ has a constant need for energy both during and between contractions.There is a growing appreciation of the diversity of mitochondria in cells and their tendency to behave collectively. Nuno Raimundo from the University of Gttingen, Germany, said that mitochondria often form distinct populations or groups of mitochondria and have different behaviors.For example, neuroscientists have noted that mitochondria can take on different appearances depending on where they are located in the neuronal landscape. The mitochondria may look like a tube or rugby ball in the middle of certain types of neurons. In spindly dendrites that receive outgoing signals from other neurons the mitochondria form long, branched networks. At the sites where outgoing signals are in axons the mitochondria look more like tennis balls. Recent research has shown that these shapes allow organelles to absorb different amounts of calcium in accordance with the various needs of the ion throughout the cell.The Analogy is Powerful EvenPicard and Sandi believe that mitochondrial social networks exist in all living things. They are evident by the numerous instances of interactivity, diversity and cooperation of organelles. These networks may extend beyond cells. Sandi said that cortisol, which is made in mitochondria from the adrenal gland, can have an effect on mitochondria elsewhere and create a long-distance way of communicating stress.Picard is a mitochondrial psychobiologist, and studies how psychological stress can manifest at the level mitochondria. The physiological consequences of this can be the sociability organelles. This is just one component of interconnectedness in life. Sociality is a result of sociality being able to produce sociality. The sociability and cooperation of mitochondria allows cells to form complex organs that are dependent on each other. Picard stated that the social nature of animals is an extension to the sociality found at the lower levels of the ladder.Even scientists who believe in the importance of studying mitochondrial interactions are hesitant to call them social. Nunnari stated that analogies have their power, but I avoid anthropomorphizing mitochondria.One problem is that the descriptions of social and cooperative suggest a level of agency that is inappropriate for organelles. Raimundo stated that it is not that they are looking for a group, but they do not want to be part of one. They were just programmed to behave that way.He also suggested that mitochondria could be seen as participants in social networks. To study mitochondria, scientists have traditionally used a reductionist approach to dissecting the genes and proteins that underpin their biology. Raimundo stated that while this research is essential to understand the details of mitochondrial interactions, it should not be the only one. Sometimes, this may mean that mitochondria must be treated as entities that can process information independently and act on it together.Health and Disease: CluesRaimundo stated that this networked view on mitochondria could also be useful in the study of signaling among different types of organelles. For decades, it has been well known that mitochondria are intimately connected to the nucleus. This is where the majority of the genes responsible for the production of mitochondrial proteins are located. It is now becoming clear that mitochondria interact with many other organelles.Some diseases are being studied by studying the networks of mitochondria. Scientists suspect that Parkinson's disease may be caused by defective energy metabolism, however, there has not been any clear evidence to support this hypothesis. Feng He, a researcher at the Luxembourg Institute of Health, directed a computer to analyze 700 gigabytes of microscopy video of Parkinson's disease patients' gut neurons. Nearly 20 features were identified that mathematically characterize the mitochondrial networks of patients with Parkinson's disease. These included their organelles density, proximity, interactions, and interconnections. Although the study was limited to a few patients, it found that these features could be used collectively to distinguish patients from healthy individuals. He believes that the mitochondrial networks involved in Parkinson's disease may be less efficient and this could lead to inefficiency. He said that network studies can help us understand different types of cells in our bodies by capturing layers of biology that are often overlooked by reductionist approaches.Picard stated that network approaches may eventually lead to new treatments. Picard already has some ideas about how to improve mitochondrial communication. He and his colleagues gave mice three hours of running and then examined the mitochondria in their lower legs muscles. They formed new connections where the organelles touched each other. This is the same type that aligns their Cristae. This could indicate that exercise promotes communication between mitochondria. Picard stated that it makes them more social.
