Available online at www.sciencedirect.com
Mitochondrial vesicles: an ancient process providing new links to peroxisomes Miguel A Andrade-Navarro1, Luis Sanchez-Pulido2 and Heidi M McBride3 The fate and function of mitochondria and peroxisomes are tightly coupled. Their biogenesis is linked through common transcriptional pathways, and their growth and division is mediated by common fission machinery. Recently, these two organelles have been linked in a much more direct manner, where mitochondrial derived vesicles deliver specific cargo into a population of peroxisomes. There are a number of concepts that emerge from this observation, including the idea that mitochondria are able to segregate their contents into vesicles and that vesicles may represent a new mechanism for mitochondrial communication with peroxisomes, and potentially other intracellular organelles. By considering the function of their bacterial relatives, we can develop hypothesis about the origin and mechanism of mitochondrial vesicle formation. The vesicles released from bacteria have numerous functions in signaling within the colony and mediating host infection. Therefore, the first observation that the mitochondria form vesicles that are transported within the cell defines a new, evolutionarily conserved process in mitochondrial cell biology and dynamics. This review will explore the mechanism and function of mitochondrial vesicle transport with an eye toward the evolutionary implications of this new pathway in cell biology. Addresses 1 Max Delbru¨ck Center for Molecular Medicine, Robert Ro¨ssle Str. 10, 13125 Berlin, Germany 2 Functional Genetics Unit, University of Oxford, Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford OX1 3QX, UK 3 University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON K1Y 4W7, Canada Corresponding author: McBride, Heidi M (
[email protected])
Current Opinion in Cell Biology 2009, 21:560–567 This review comes from a themed issue on Membranes and organelles Edited by Greg Odorizzi and Peter Rehling Available online 5th May 2009 0955-0674/$ – see front matter # 2009 Elsevier Ltd. All rights reserved. DOI 10.1016/j.ceb.2009.04.005
highlighted the reticular, interconnected nature of the mitochondrial population within cells [2]. With the exception of the contacts between the mitochondria and the endoplasmic reticulum [3,4], there have been only limited investigations into how mitochondria may be in contact with any other intracellular organelles. There are a number of important reasons why the mitochondrial reticulum may need to establish direct means of communication with other organelles. For example, there are regulated interactions between the endosome and mitochondrial compartments for the direct transport of ions like iron [5,6]. The mitochondria also have a close metabolic relationship with the peroxisomes, which share the task of degrading fatty acids [7]. In most plants and fungi, the peroxisomes perform this task exclusively, but in mammalian cells the mitochondria have taken over most fatty acid catabolism. Importantly, a number of very long chain or modified fatty acid species cannot be degraded by the mitochondria and must be transported instead into the peroxisomes [7]. On the contrary, straight-chain fatty acids within the peroxisomes cannot be fully degraded there and must return to the mitochondria. In this way, there is some fatty acid flux between these two organelles to facilitate their complete oxidation. In addition to fatty acid metabolism, the detoxifying role for the peroxisomes parallels that of the mitochondria, with both organelles actively reducing cellular peroxides and superoxides [8]. The dual control over ROS and b-oxidation pathways means that they are functionally highly interconnected. It is therefore not surprising that their biogenesis is also controlled through a common signaling cascade regulated by the peroxisome proliferator-activated receptor gamma, coactivator 1 (PGC1a) [9,10]. Finally, their biogenesis is further linked since the division of growing peroxisomes and mitochondria requires common machinery, with at least four of the core components of this pathway acting upon both organelles [11]. These include the cytosolic dynamin-related protein, DRP1 [12–17], and Mdv1p [18], along with the two integral membrane proteins fission factor 1, Fis1 [19,20] and mitochondrial fission factor, Mff [21]. From all this, it is clear that these two organelles are coordinately regulated through multiple mechanisms.
Introduction
Mitochondrial derived vesicles carry specific cargo to the peroxisomes
The mitochondria have a central role in cellular metabolism, and the last decade has seen profound changes in our appreciation for the dynamic and integrated nature of this organelle [1]. Studies into homotypic mitochondrial fusion, and the regulation of mitochondrial fission have
Recently, yet another means through which these two organelles appear to communicate was uncovered. Through the characterization of a new mitochondrial anchored protein ligase (MAPL, also called MULAN [22]), it was observed that this mitochondrial protein
Current Opinion in Cell Biology 2009, 21:560–567
www.sciencedirect.com
