Retrograde signals from endosymbiotic organelles: a common control principle in eukaryotic cells

Abstract

Endosymbiotic organelles of eukaryotic cells, the plastids, including chloroplasts and mitochondria, are highly integrated into cellular signalling networks. In both heterotrophic and autotrophic organisms, plastids and/or mitochondria require extensive organelle-to-nucleus communication in order to establish a coordinated expression of their own genomes with the nuclear genome, which encodes the majority of the components of these organelles. This goal is achieved by the use of a variety of signals that inform the cell nucleus about the number and developmental status of the organelles and their reaction to changing external environments. Such signals have been identified in both photosynthetic and non-photosynthetic eukaryotes (known as retrograde signalling and retrograde response, respectively) and, therefore, appear to be universal mechanisms acting in eukaryotes of all kingdoms. In particular, chloroplasts and mitochondria both harbour crucial redox reactions that are the basis of eukaryotic life and are, therefore, especially susceptible to stress from the environment, which they signal to the rest of the cell. These signals are crucial for cell survival, lifespan and environmental adjustment, and regulate quality control and targeted degradation of dysfunctional organelles, metabolic adjustments, and developmental signalling, as well as induction of apoptosis. The functional similarities between retrograde signalling pathways in autotrophic and non-autotrophic organisms are striking, suggesting the existence of common principles in signalling mechanisms or similarities in their evolution. Here, we provide a survey for the newcomers to this field of research and discuss the importance of retrograde signalling in the context of eukaryotic evolution. Furthermore, we discuss commonalities and differences in retrograde signalling mechanisms and propose retrograde signalling as a general signalling mechanism in eukaryotic cells that will be also of interest for the specialist. This article is part of the theme issue 'Retrograde signalling from endosymbiotic organelles'.

Keywords: chloroplasts; intracellular communication; metabolites; mitochondria; plastids; signalling.

Figure 1.

Establishment of retrograde control during the evolution of eukaryotes. The diagram depicts the major steps in the evolutionary acquisition of mitochondria and plastids by eukaryotes. Rectangles represent endosymbiotic host cell or eukaryotic host cell, respectively. Ovals represent bacterial ancestors and resulting endosymbionts as well as final plastids. Final mitochondria are represented by small icons with brown outer and blue inner membrane. DNA of endosymbionts is represented by blue circles and gene transfer to the nucleus by black arrows. The reduction of coding capacity is indicated by the reduced size of DNA-representing circles. Continuous light-blue arrows: anterograde signalling. Broken light blue arrows: retrograde signalling. Large connecting arrows in grey, green and red represent the evolutionary lines. Yellow circles represent the respective import machineries. Note that retrograde signalling from mitochondria was likely to be established when plastids evolved. Basic principles should have been conserved in the different evolutionary lines. Further evolution of mitochondrial retrograde signals in autotrophs, however, was probably influenced by the presence of plastids (double-headed arrow, ‘interaction?’). In heterotrophs, other influences such as multicellularity and tissue context may have generated different evolutionary constraints. In Rhodophyta (pink box) and Chlorophyta (green box), mitochondria, plastids and the nucleus developed triangular signalling networks.

Figure 2.

Common principles in retrograde signalling of eukaryotic organelles. The diagram depicts four major biological triggers (indicated in the left panel) in which mitochondria and chloroplasts (represented by head-to-head orange and green ovals as a combined symbol) initiate retrograde signal classes with high similarity in signal identity (pink triangle), gene target and cellular response (depicted in the right panel). Organelles detect and integrate external or cellular triggers (yellow arrows, input integration), and produce the corresponding retrograde signal(s) (pink arrow) that is/are detected by the nucleus, where the information is finally integrated to initiate a corresponding response (blue arrows, output integration). ETC, electron transport chain; ROS, reactive oxygen species; OXPHOS, oxidative phosphorylation; UPR, unfolded protein response.