Modes and mechanisms for the inheritance of mitochondria and plastids in pathogenic protists

Abstract

Pathogenic protists are responsible for many diseases that significantly impact human and animal health across the globe. Almost all protists possess mitochondria or mitochondrion-related organelles, and many contain plastids. These endosymbiotic organelles are crucial to survival and provide well-validated and widely utilised drug targets in parasitic protists such as Plasmodium and Toxoplasma. However, mutations within the organellar genomes of mitochondria and plastids can lead to drug resistance. Such mutations ultimately challenge our ability to control and eradicate the diseases caused by these pathogenic protists. Therefore, it is important to understand how organellar genomes, and the resistance mutations encoded within them, are inherited during protist sexual reproduction and how this may impact the spread of drug resistance and future therapeutic approaches to target these organelles. In this review, we detail what is known about mitochondrial and plastid inheritance during sexual reproduction across different pathogenic protists, often turning to their better studied, nonpathogenic relatives for insight.

Fig 1. A phylogenetic tree of eukaryotes showing the variety of endosymbiotic organelles in pathogenic and nonpathogenic protists.

The main lineages are redrawn according to Keeling and Burki (2019) and Husnik and colleagues (2021) and are depicted according to current consensus phylogeny [74,75]. Protists and organelles are hand-painted by Sarah N. Farrell. Clades and supergroups of interest are highlighted in colour. Each protist contains a nucleus (or a micronucleus and macronucleus in Ciliata) and endosymbiotic organelles. Organelles are colour coded according to the legend at the bottom of the figure. Classical mitochondria (yellow) can contain either linear or circular organellar genomes (as specified for each protist in Table 1 and the body text). Hydrogenosomes (orange) may also contain a linear genome or lack a mitochondrial genome entirely. The mitochondrion of Trypanosoma and Leishmania contains kinetoplast DNA (kDNA) comprised of DNA minicircles and maxicircles (red).

Fig 2. Mechanisms used to achieve uniparental (maternal) inheritance and the probability of paternal leakage or biparental inheritance.

This model details the mechanisms commonly used to achieve uniparental (maternal) organellar inheritance of mitochondria and plastids at distinct time points during sexual reproduction, as previously reported (reviewed in [,,,,–90]). The orange ramp at the bottom represents our proposal that mechanisms implemented earlier in sexual reproduction should more effectively prevent paternal leakage than those during or after fertilisation. In other words, late mechanisms are potentially more prone to failure resulting in leakage of male derived organelles into sexually produced offspring.

Fig 3. Pathogenic protists with unknown sexual cycles and mitochondrial and plastid inheritance patterns during mating.

This figure illustrates the endosymbiotic organelles found in each protist. Protists and organelles are hand-painted by Sarah N. Farrell. Mitochondria (yellow) contain either circular or linear genomes as depicted. Hydrogenosomes (orange) and mitosomes (purple) do not contain an organellar genome. Euglena plastids (green) possess a circular genome. References are provided in brackets below the text where relevant.

Fig 4. Nonpathogenic protists with known sexual cycles but unstudied mitochondrial and plastid inheritance patterns.

Protists and organelles are hand-painted by Sarah N. Farrell. Within the group Ciliata, some ciliates contain hydrogenosomes (orange) with linear genomes (e.g., N. ovalis) while others possess classical mitochondria (yellow) with linear genomes (e.g., P. aurelia). Dinoflagellates possess both mitochondria and plastids (green), each harbouring their own genome. Potential mechanisms for uniparental inheritance in these groups include exclusion (E) and sequestration (S). References are provided in brackets below the text where relevant.

Fig 5. Pathogenic protists with known sexualities and better studied organellar inheritance patterns.

This figure illustrates the endosymbiotic organelles and presence or absence of an organellar genome within each listed protist. Protists and organelles are hand-painted by Sarah N. Farrell. Organellar genomes are linear or circular as depicted. While many apicomplexans possess both an apicoplast (green) and a classical mitochondrion (yellow), Cryptosporidium and the eugregarines instead contain a single mitosome (purple) and no apicoplast. The mitochondrion found in Trypanosoma and Leishmania (red) harbours kinetoplast DNA comprised of DNA minicircles and maxicircles. (P) = plastid, (M) = mitochondria. Different mechanisms such as selective degradation of organellar DNA (SD), degradation of whole organelle structures (D) and exclusion (E) are used to ensure uniparental inheritance. References are provided in brackets below the text where relevant.