Aerobic kinetoplastid flagellate Phytomonas does not require heme for viability

Abstract

Heme is an iron-coordinated porphyrin that is universally essential as a protein cofactor for fundamental cellular processes, such as electron transport in the respiratory chain, oxidative stress response, or redox reactions in various metabolic pathways. Parasitic kinetoplastid flagellates represent a rare example of organisms that depend on oxidative metabolism but are heme auxotrophs. Here, we show that heme is fully dispensable for the survival of Phytomonas serpens, a plant parasite. Seeking to understand the metabolism of this heme-free eukaryote, we searched for hemecontaining proteins in its de novo sequenced genome and examined several cellular processes for which heme has so far been considered indispensable. We found that P. serpens lacks most of the known hemoproteins and does not require heme for electron transport in the respiratory chain, protection against oxidative stress, or desaturation of fatty acids. Although heme is still required for the synthesis of ergosterol, its precursor, lanosterol, is instead incorporated into the membranes of P. serpens grown in the absence of heme. In conclusion, P. serpens is a flagellate with unique metabolic adaptations that allow it to bypass all requirements for heme.cytochromes | respiration | sterols | protist

Mitochondrial ClpX Activates a Key Enzyme for Heme Biosynthesis and Erythropoiesis

“…Nearly all organisms (with a few known exceptions among parasites) require heme for viability (Koreny et al, 2012), and most organisms synthesize heme endogenously. Heme is an essential cofactor for many enzymes, including several members of the respiratory chain, p450 enzymes, and sterol biosynthetic enzymes, and also acts as the sensor component of multiple environmentally responsive transcription factors (Girvan and Munro, 2013; Hamza and Dailey, 2012).…”

Distinct Prominent Roles for Enzymes of Plasmodium berghei Heme Biosynthesis in Sporozoite and Liver Stage Maturation

“…Thus, heme mediates fundamental biological processes, including oxygen transport, antioxidant responses, and cellular respiration, and is, therefore, indispensable for virtually all living organisms. Exceptions, like the parasitic kinetoplastid flagellate Phytomonas serpens that can survive in the complete absence of heme (2), are rare. As a result of this nearly universal dependence on heme, two complementary strategies for heme acquisition have evolved; heme scavenging and de novo heme biosynthesis.…”

Giardia intestinalis Incorporates Heme into Cytosolic Cytochrome b 5

“…It is tempting to speculate that G. intestinalis may compete for heme with enterocytes that are able to take up intact heme as a source of iron (54). However, the utilization of exogenous heme by parasitic protists has been experimentally assessed only in certain trypanosomatids (56)(57)(58)(59). Moreover, the mechanisms for heme acquisition and its transport in trypanosomatids are poorly understood and are virtually unknown in other parasitic protists.…”

“…Therefore, either the heme requirements of Giardia fall below a concentration of 8 nM or heme may not be essential for parasite growth in vitro. Thus far, the kinetoplastid Phytomonas serpens is the only eukaryote that has been found to be able to survive entirely without heme (59). Similar to Giardia and other anaerobes, P. serpens lacks most of the known hemoproteins, although it is a protist with aerobic metabolism.…”

“…Similar to Giardia and other anaerobes, P. serpens lacks most of the known hemoproteins, although it is a protist with aerobic metabolism. However, P. serpens possesses unique metabolic adaptations that allow it to bypass the functions of proteins that are dependent on heme (59). Interestingly, group II cytb 5 appears to be the only heme-binding protein that is encoded in the P. serpens genome.…”