Elsevier

Mitochondrion

Volume 11, Issue 5, September 2011, Pages 814-819
Mitochondrion

Review
Mitochondrial activity, embryogenesis, and the dialogue between the big and little brains of the cell

https://doi.org/10.1016/j.mito.2010.11.002Get rights and content

Abstract

While it is clear that mitochondria play integral roles in cellular homeostasis, adaptation, cellular and survival, recent studies suggest possible roles for mitochondria as modulators of what were previously considered cytoplasmic/nuclear signaling systems. Embryonic patterning has been linked to asymmetries in mitochondria-based respiratory activity. As outlined by Coffman (2009), defining the role of mitochondria as modulators of embryonic patterning is inherently difficult, given their essential metabolic roles. This review attempts to place mitochondrial-transcription factor interactions in the context of the early development of the tetrapod Xenopus laevis, where a number of the proteins and signaling systems known to play critical roles in embryonic patterning, e.g. β-catenin, NF-κB, p53, and STAT3, have been found to localize to mitochondria.

Introduction

There is an old, and more recent literature that implicates early embryonic asymmetries in developmental patterning and tissue specification (see Coffman, 2009, Coffman and Denegre, 2007 for reviews). For example, Barth (1944) reported differences in O2 consumption between different regions of the Amblyostoma punctatum (newt) embryo, while Marinos et al. (Marinos, 1986) and Yost et al. (1995) found asymmetries in mitochondrial numbers between the dorsal and ventral sides of the early Xenopus laevis (clawed frog) embryo. The Xenopus oocyte contains ~ 107 mitochondria (Marinos and Billett, 1981), which are originally arranged asymmetrically (Klymkowsky and Karnovsky, 1994). As oogenesis proceeds, one mitochondrial population remains associated with the germinal vesicle (the oocyte nucleus), while the other migrates with the germ plasm to the vegetal cortex/vegetal pole of the oocyte (Mignotte et al., 1987, Dent and Klymkowsky, 1989) (Fig. 1A). Cytoplasmic movements following sperm entry are known to play a critical role in the specification of the dorsal-anterior and ventral-posterior axes (Danilchik and Denegre, 1991, Vincent et al., 1986, Vincent and Gerhart, 1987). Fertilization-induced cytoplasmic reorganization then interacts with other maternally established asymmetries in Sox- and T-Box type transcription factors, Wnt signaling, and NF-κB, Nodal and Bone Morphogenic Protein (BMP)1 activities to further pattern the early embryo (Fig. 1).

Asymmetries in mitochondrial distribution may be expected to generate asymmetries in respiratory activity, which have been reported (Barth, 1944). On the other hand, using C14 labeled molecules (e.g. glucose and pyruvate, among others), Thoman and Gerhart (1979) found no apparent difference in metabolic activity between dorsal and ventral regions of X. laevis embryos. This leads us to consider other types of effects, associated with mitochondria. Here there are hints from recent studies in the sea urchin, where Coffman and colleagues (Coffman et al., 2009, Coffman and Davidson, 2001, Coffman et al., 2004) found evidence for a patterning role for reactive oxygen species (ROS). These are known to influence a number of signaling system (Coffman and Denegre, 2007, Covarrubias et al., 2008, Daiber, 2010, Dennery, 2007, Sun and Oberley, 1996). As an example, it is clear that NF-κB activity is influenced by ROS (see Glineur et al., 2000) and that NF-κB is required for normal mesoderm and neural crest formation in Xenopus (see Zhang et al., 2006 and references therein). That said, treatment of Xenopus embryos with the herbicide paraquat, which is known to increase ROS levels, does not dramatically influence either mesoderm or neural crest formation; it does, however, generate later stage defects in somites and myotomal muscle (Vismara et al., 2006), both mesodermal derivatives.

Section snippets

Thinking about mitochondrial–“host” interactions

Mitochondria are generally introduced to students during courses in cell biology. In the typical classroom, their endosymbiotic origins and role in aerobic respiration and ATP synthesis are typically stressed, but more recently their roles in the regulation of apoptosis, as well as intracellular [Ca2+] regulation, hypoxic signaling (Poyton et al., 2009a, Poyton et al., 2009b), nitric oxide production (Castello et al., 2006, Castello et al., 2008, Ghafourifar and Cadenas, 2005), and the

Reflections on localization studies

In general, the observation that provides the initial clue of mitochondrial involvement in various signaling/cellular response systems is the localization of relevant proteins to mitochondria or the mitochondrial fraction of cells. In this light, past studies on cytoskeletal/cell adhesion proteins can be illuminating. A classic example is the presence of actin and myosin within nuclei. Experimental studies using the Xenopus oocyte nuclei by Scheer et al. (1984) provided strong evidence for a

Bcl-2

My own interest in the role of mitochondria in the regulation of embryonic signaling began with a somewhat surprising result obtained in the course of studies on the role of the zinc-finger transcription factor Slug (Snail2) in Xenopus (Zhang et al., 2006, Carl et al., 1999). Snail2/Slug and the related protein Snail (Snail1) have been implicated in both the regulation of epithelial–mesenchymal transition (EMT) and apoptosis (Locascio et al., 2002). To disconnect these two functions, we

Summary

At this point, what is clear is that i) mitochondrial activity, particularly in the form of ROS/RNS can influence the activities of a wide range of proteins and signaling systems, ii) proteins not expected to be present in mitochondria have been found there (and vice versa); and iii) some of these observations will turn out to be molecular noise or epiphenomena, of little or subtle physiological significance, while others may be critical. The trick, experimentally, will be to examine what

Acknowledgement

Our work has been supported by grants from the NIH (GM 54001 and GM84113) and inspired by the unexpected weirdness of nature. We beg for forgiveness for limiting the scope of our review.

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