Mitochondria and Cell Death

242 Pages·2016·6.59 MB·English

by  David M. Hockenbery (eds.)

Cell Death in Biology and Diseases
David M. Hockenbery Editor
Mitochondria
and Cell
Death
Cell Death in Biology and Diseases

Series Editors
Xiao-Ming Yin
Zheng Dong
More information about this series at h ttp://www.springer.com/series/8908

David M. Hockenbery
Editor
Mitochondria and Cell Death
Editor
David M. Hockenbery
Clinical Research Divison
Fred Hutchinson Cancer Research Center
Seattle , WA , USA
Cell Death in Biology and Diseases
ISBN 978-1-4939-3610-6 ISBN 978-1-4939-3612-0 (eBook)
DOI 10.1007/978-1-4939-3612-0
Library of Congress Control Number: 2016934848
© Springer Science+Business Media New York 2016
T his work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
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Series Preface
C ell death, or conversely cell survival, is a major biological phenomenon. Just as
with cell proliferation and cell differentiation, cell death is a choice that a cell has to
make, sometimes voluntarily, other times accidentally. As such, cell death serves a
purpose in the biology of a multicellular organism. The machinery of cell death and
that of cell protection are evolutionarily conserved and their elements can even be
found in single-celled organisms. The disruption of cell death mechanisms can
often cause developmental abnormalities. Factors that can trigger cell death are
diverse, and the cell death process is intricately connected with other biological
processes. Cell death directly contributes to the pathogenesis of many diseases,
including cancer, neurodegenerative diseases, and tissue injury in organ failure.
The study of cell death and cell survival has become a multidisciplinary subject,
which requires expertise from all the fi elds of modern biology. Exploring the role of
cell death in disease development and the modulation of cell death for the preven-
tion and treatment of devastating disease demands constant updating of our knowl-
edge through the broadest interactions among all investigators, basic and clinical.
The rapid expansion of our knowledge in this fi eld has gone beyond what could be
summarized in a single book. Thus, this timely series C ell Death in Biology and
Diseases summarizes new developments in different areas of cell death research in
an elaborate and systemic way. Each volume of this series addresses a particular
topic of cell death that either has a broad impact on the fi eld or has an in-depth
development in a unique direction. As a whole, this series provides a current and
encyclopedic view of cell death.
W e would like to sincerely thank the editors of each volume in the series and
the authors of each chapter in these volumes for their strong commitment and
great effort towards making this mission possible. We are also grateful to our
team of professional Springer editors. They have worked with us diligently and
v
vi Series Preface
creatively from the initiation and are continuing this on the development and
production of each volume of the series. Finally we hope that the readers will
enjoy the reading, fi nd the content helpful to their work, and consider this series
an invaluable resource.
Indianapolis, IN, USA Xiao-Ming Yin, M.D., Ph.D.
Augusta, GA, USA Zheng Dong, Ph.D.
Pref ace
This volume provides an in-depth, up-to-date collection of papers on mitochondrial
biology in the context of the cellular environment, and the roles of mitochondria in
cell death and the various cellular programs that can intersect with cell death path-
ways (intracellular signaling, homeostasis, and pathogen resistance). There has
been a surge in interest in mitochondrial functions in the last 5 years, with substan-
tial new understanding in the areas of mitochondrial organelle and protein homeo-
stasis, mitochondrial dynamics, interorganelle associations, and integration within
diverse cellular programs. This progress has led to novel insights into the important
place of mitochondria in orchestrating these programs. The importance of mito-
chondrial dysfunction in pathogenesis of clinical diseases, including neurodegen-
erative diseases, cancer, metabolic syndrome, and aging, illustrates the strong
relevance of these topics in “bench to bedside” investigations. The chapter authors
are renowned experts in their fi elds, actively contributing to the expansion of mod-
ern mitochondrial research.
T he earliest and best known function of mitochondria, generation of ATP from
proton motive force, led to the recognition that the same electrochemical gradient
could be used to move other ions and metabolites. The study of mitochondrial Ca 2+
transport revealed the permeability transition, initially in isolated mitochondria, but
later confi rmed in situ and its role in the clinical setting of ischemia-reperfusion
injury and necrotic cell death. Fontaine and Bernardi discuss current conceptions of
the permeability transition pore and the evidence for physiological functions in Ca 2+
handling. Among the recent advances in mitochondrial biology is the functional
identifi cation of new mitochondrial proteins. Boyman, Williams, and Lederer pro-
vide a detailed review of mitochondrial Ca2 + , with special emphasis on the recently
identifi ed Ca2 + uniporter, MCU, and Na + /Ca2 + exchanger, NCLX, and the patho-
physiology of ischemia/reperfusion injury.
The central role of mitochondria in apoptotic cell death was fi rst suggested by
the novel localization of Bcl-2 oncoproteins to mitochondria. Bcl-2 proteins regu-
late mitochondrial outer membrane permeabilization (MOMP) with release of cyto-
chrome c and other p roteins with second functions as proapoptotic factors from the
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intermembrane space. Flanagan, Lucantoni, and Prehn describe the unique features
of this mitochondrial compartment and the intersecting lethal roles of resident pro-
teins once relocated to the nucleocytoplasm. Current understanding of the mecha-
nism of BAX/BAK- dependent MOMP and important remaining questions are
reviewed by Edlich and Martinou. Microscopic techniques have provided key
insights into remodeling of the mitochondrial network and cristae topology during
apoptosis, and Perkins and Ellisman discuss the emerging roles of mitochondrial
fi ssion and fusion GTPases in the mechanism(s) of cytochrome c release.
The majority of reactive oxygen species (ROS) produced in a cell originate in
mitochondria. Although ROS can damage proteins, lipids, and DNA in cells and
have been implicated in aging, chronic infl ammatory states, and cancer, healthy
cells utilize ROS in signaling pathways. The detailed understanding of ROS sig-
naling and its role in cell growth, longevity, and stress resistance, and how sig-
naling strength is regulated, are under active investigation. Allen and Spitz
provide a global perspective on these functions and the key factors involved in
maintaining physiological balancing of the oxidant/antioxidant arms of these
pathways.
M itochondria are the only organelles with their own genome (mtDNA), with
less developed DNA repair pathways and the added issue of heteroplasmy com-
pared to the nuclear chromosomes. Valente and Bielas discuss the universal exis-
tence of “microheteroplasmy” with ultrasensitive mutation assays, the need for a
new functional defi nition of homoplasmy, and the relevance of mtDNA mutations
to cancer. Quality control is also required for the mitochondrial proteome in an
oxidizing environment, and Germain reviews the recent progress in mapping the
mitochondrial unfolded protein response, UPRm t, in mammalian cells. Raimundo,
Fernandez-M osquera, and Yambire present a conceptual framework for mitochon-
drial signaling, including communication with other organelles in addition to mito-
chondria-to-nucleus regulation of gene expression.
O ne of the newest, and unexpected, roles for mitochondria is in innate antiviral
immunity. Thomas and Gale describe the generation of “innate immune synapses”
by mitochondria and mitochondria-associated membranes (MAM), as well as the
varied strategies of viruses to disable this signaling platform. Finally, Oberst, Ichim,
and Tait present an intriguing hypothesis of the evolutionary history of cytochrome
c as a pathogen-associated molecular pattern (PAMP) associated with ancestral
bacterial endosymbionts, linking MOMP in apoptosis to innate immune sensors,
with the additional possibility of graded responses to MOMP producing nonlethal
effects.
The intended audience for this book is students, new and established researchers,
and others interested in learning about the fascinating fi eld of mitochondrial biol-
ogy. Although impressive progress has been made recently, important questions in
mitochondrial biology remain unanswered, and the recruitment of new investigators
to this fi eld has been a critical component of recent discoveries. It is hoped that this
book will stimulate future scientists to join this effort.
Preface ix
I , personally, would like to acknowledge the support and guidance of my mentor,
the late Stanley Korsmeyer, who laid much of the early groundwork for the explo-
sion of interest in mitochondria and apoptotic cell death. I am grateful to the
c o-e ditors of the Cell Death in Biology and Diseases series from Springer, Xiao-
Ming Yin and Zheng Dong, for their help in the conception of this book, and Joseph
Quatela and Aleta Kalkstein from Springer for their editorial efforts.
Seattle, WA, USA David M. Hockenbery