Kukat C, Davies KM, Wurm CA, Spar H, Bonekamp NA, Kühle I, Joos F, Polosa PL, Park CB, Posse V, Falkenberg M, Jakobs S, Kühlbrandt W, and Larsson NG
Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid
PNAS 112 (36):11288–11293 (2015); doi: 10.1073/pnas.1512131112
Scientists from the Max Planck Institute for Biology of Ageing (MPI AGE) in Cologne, the Max Planck Institute of Biophysics (MPI BP) in Frankfurt a.M., and the Max Planck Institute for Biophysical Chemistry (MPI BPC) in Göttingen have gained fundamental insights into the organization of mitochondrial DNA (mtDNA). The researchers observed in high-resolution images gained with nobel prize-winning microscopy techniques that single copies of mtDNA are packaged by a specialized protein into slightly elongated structures of circa 100 nm in length.
Mitochondria are described as cellular power plants, because they produce energy in nearly every cell in the (human) body. They harbor their own genome, the mitochondrial DNA or mtDNA. The mtDNA is organized together with specific proteins in complexes inside mitochondria, the so called mitochondrial nucleoids. “The structure of these nucleoids is poorly understood. We can visualize them in the microscope, but we quickly reach the limits of conventional light microscopy when we want to look at finer structures”, says Christian Kukat, researcher at the Max Planck Institute for Biology of Ageing in Cologne. “Therefore we asked for help from other Max Planck Institutes.”
Scientists from the Max Planck Institute in Göttingen and Frankfurt use the latest microscopy techniques, which can bypass the resolution limit of the conventional light microscopy. With the help of super-resolution STED microscopy, electron microscopy (EM) and electron cryo-tomography (cryo-ET) they characterized the ultrastructure of the mam malian mitochondrial nucleoid. “We saw that nucleoids have an irregular, ellipsoidal shape and contain typically just a single copy of mitochondrial DNA. Even if the cell has more mtDNA molecules, the nucleoid ultrastructure remains the same”, says Kukat. The other mtDNA molecules are packaged into additional nucleoids.
These insights of the researchers from three Max Planck Institutes establish a new basis for the investigation of diseases that are inherited mitochondrially, from mothers to the offspring. Christian Kukat: “In future we will continue our studies on the connection of mitochondria and the processes of ageing.”
Image above: 3D model/tomographic volume of a bovine heart mitochondrion. Segmented surface representation showing position of mitochondrial nucleoids (green) in a bovine heart mitochondrion. Green: nucleoids, gray: outer membrane, grayblue: cristae. Credit: MPI BP Frankfurt a.M. / Karen Davies and Proceedings of the National Academy of Sciences of the United States of America (PNAS).