ReviewMitochondrial retrograde regulation in plants
Introduction
Abiotic stresses, biotic stresses, or mutations can alter the functioning of organelles. In response, organelles can direct changes in nuclear gene expression. The alteration of nuclear gene expression directed by organelles through organelle-to-nucleus signaling is referred to as retrograde communication, retrograde signaling, retrograde stress signaling or retrograde regulation (Butow and Avadhani, 2004, Liao and Butow, 1993, Patil and Walter, 2001, Rhoads and Vanlerberghe, 2004, Rodermel, 2001, Surpin et al., 2002). In the case of plant mitochondria-to-nucleus signaling, we refer to it as mitochondrial retrograde regulation (MRR). Signaling due to changes in mitochondrial function could link to metabolic signaling pathways or general reactive oxygen species (ROS) signaling pathways and trigger gene expression responses, but these would still be mitochondria-directed responses. Mounting evidence indicates that retrograde regulation is an important regulatory/response mechanism for plants, animals and fungi. This is a new but rapidly expanding area of biology. Relatively little attention has been given to retrograde regulation in plants especially to MRR.
In animals, mitochondrial dysfunction, and the MRR that likely results, is now thought to be an important factor in many human diseases (Butow and Avadhani, 2004, Lane, 2006, Weissig et al., 2004). Mitochondrial dysfunction, and in some cases MRR, has been connected to Alzheimer’s disease (Moreira et al., 2006, Parihar and Brewer, 2007), Parkinson’s disease (Beal, 2005, Kwong et al., 2006), Huntington’s disease (Beal, 2005, Kwong et al., 2006, Marx, 2005), bipolar disorder (Iwamoto et al., 2005, Kato, 2005), schizophrenia (Ben-Shachar and Laifenfeld, 2004, Iwamoto et al., 2005), type 2 diabetes (Guo et al., 2005, Lowell and Shulman, 2005), cancer ( Butow and Avadhani, 2004, Singh et al., 2005), and aging (Beal, 2005, Butow and Avadhani, 2004). MRR is a relatively new angle on the importance of mitochondria in diseases (Biswas et al., 2005, Butow and Avadhani, 2004, Singh et al., 2005).
Although some target genes are in common among MRR pathways, there seem to be several distinct MRR signaling pathways in animals (Butow and Avadhani, 2004).
MRR in yeast has been well studied. The yeast Saccharomyces cerevisiae responds to mitochondrial dysfunction by altering nitrogen and carbon metabolism (Butow and Avadhani, 2004). Respiratory deficient cells shift metabolism in an attempt to maintain glutamate levels by restoring levels of TCA cycle intermediates. Gene induction involves regulation by RTG transcription factors in many of the best studied cases (Butow and Avadhani, 2004, Poyton and McEwen, 1996, Sekito et al., 2000), but at least two other MRR signaling pathways are present in S. cerevisiae (Devaux et al., 2002, Guaragnella and Butow, 2003).
Plants contain two energy-producing organelles: chloroplasts, which convert sunlight to chemical energy in the form of ATP and stored energy in the form of carbon compounds such as sugars and lipids, and mitochondria, which convert stored energy to ATP. Both organelles are able to communicate with the nucleus. Chloroplastic retrograde regulation pathways are, to date, the best studied retrograde signaling pathways in plants. Potential pathways have been identified for signaling in response to photomorphogenesis (Surpin et al., 2002), altered function during chloroplast biogenesis (Barr et al., 2004), and redox poise (Rodermel, 2001). In this review, we focus on our current understanding of MRR in plants, which has been revealed primarily in instances of mitochondrial dysfunction. Mitochondrial dysfunction caused by mutations in plants often results in male sterility, in an embryo lethal phenotype, or in chlorotic plants that do not survive to maturity (Newton et al., 2004). In addition, mitochondrial dysfunction in plants can be caused by abiotic and biotic stresses. Although relatively little is known about the specific cellular consequences of mitochondrial dysfunction in plants, there is growing evidence that the responses of mitochondria to biotic and abiotic stresses contribute significantly to overall plant stress responses. The molecular mechanisms used by retrograde signaling pathways have just begun to be defined; a few components have been identified in some cases. Mitochondria likely play vital roles in stress responses by contributing to altered nuclear gene expression. A great deal of flexibility in responses to stresses is especially important for plants because they are sessile and these changes in nuclear gene expression likely contribute to this flexibility. The responses of mitochondria to stresses, including the specific target genes of MRR in individual stress responses, may determine the fate of plant cells, resulting in either recovery or cell death (Fig. 1).
Section snippets
MRR from chemical disruption of mitochondrial function and in mitochondrial mutants
In plants, some fungi, some animals, and some protozoans the mitochondrial electron transport chain (mtETC) consists of two, partially overlapping respiratory pathways: the cytochrome respiratory pathway which has cytochrome oxidase (COX) as the terminal oxidase and the alternative respiratory pathway, which has alternative oxidase (AOX) as the terminal oxidase (Finnegan et al., 2004, Mackenzie and McIntosh, 1999, McDonald and Vanlerberghe, 2004, Siedow, 1995, Siedow and Umbach, 1995,
MRR in response to abiotic stresses
Plant mitochondria may function as general sensors of stresses and initiate cellular responses to specific stresses, or, at least contribute to the overall response to a given stress (Fig. 1; Jones, 2000). This may include both responses to abiotic stresses and biotic stresses.
MRR in response to biotic stresses
Although the precise roles have not yet been elucidated, there is evidence for the importance of plant mitochondria during pathogen attack, including the involvement of MRR. Increased respiration during pathogen attack has been documented (Baker et al., 2000, Baker et al., 2001). This may be due to the need for increased energy during infection, but it may also result in increased mtROS production resulting from an inhibition of respiration caused by the pathogen during the infection. Again,
ROS are involved in plant MRR associated with mtETC disruption
It is clear that a dramatically increased cellular ROS level is a common feature of abiotic and biotic plant stresses and that an increased cellular ROS level causes altered nuclear gene expression (Inzé and Van Montagu, 1995, Jones, 2000, Kubo et al., 1999, Kuzniak and Urbanek, 2000, Taylor et al., 2002, Vranová et al., 2002). However, the precise roles of ROS in plant stress responses and the role(s), if any, of ROS in all types of MRR are not clear. ROS are both potential damaging compounds
MRR and the choice between recovery and programmed cell death
Apoptosis is a form of PCD that has defined cell morphological changes and, in animals, can clearly be directed by mitochondria (Green and Reed, 1998). Recently it was shown that mammalian cells responding to mitochondrial dysfunction with MRR are more resistant to apoptosis due to induced expression of anti-apoptotic proteins, suggesting that these events are directly connected in animals (Biswas et al., 2005). Several studies indicate that mitochondria can direct at least some forms of PCD in
Multiple MRR pathways in plants
Compelling evidence suggests that multiple types of mitochondrial signaling pathways exist in plants (Djajanegara et al., 2002, Gray and McIntosh, 1998, Karpova et al., 2002, Kuzmin et al., 2004, Zarkovic et al., 2005). These include the observation that citrate addition (which is assumed to affect mitochondrial function) induces AOX gene expression in both suspension-cultured tobacco cells and suspension-cultured soybean cells, but does not cause detectable increases in ROS (Djajanegara et
Summary
Plant cells must react to a variety of adverse environmental conditions that they may experience on a regular basis. Part of this response centers around (1) ROS as damaging molecules and signaling molecules; (2) redox status, which can be influenced by ROS production; (3) energy status; and (4) availability of metabolites. All of these are also likely to interface with changes in hormone levels (Desikan et al., 2005, Kwak et al., 2006). Each of these areas can be strongly influenced by changes
Acknowledgements
We thank Dr. Ann L. Umbach for helpful discussions and critical reading of this manuscript and Samuel J. White for help with manuscript preparation.
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