Mitochondrial outer membrane proteome of Trypanosoma brucei reveals macromolecular transport machineries and novel factors required to maintain mitochondrial morphology

The mitochondrial outer membrane (MOM) separates the mitochondria from the cytoplasm, serving both as a barrier and as a gateway. Protein complexes — believed to be universally conserved in all eukaryotes — reside in the MOM to orchestrate and control metabolite exchange, lipid metabolism and uptake of biopolymers such as protein and RNA. African trypanosomes are the causative agent of the sleeping sickness in humans. The parasites are among the earliest diverging eukaryotes that have bona fide mitochondria capable of oxidative phosphorylation. Trypanosomes have unique mitochondrial biology that concerns their mitochondrial metabolism and their unusual mitochondrial morphology that differs to great extent between life stages. Another striking feature is the organization of the mitochondrial genome that does not encode any tRNA genes, thus all tRNAs needed for mitochondrial translation have to be imported. However, the MOM of T. brucei is essentially unchartered territory. It lacks a canonical protein import machinery and facilitation of tRNA translocation remains completely elusive. Using biochemical fractionation and label-free quantitative mass spectrometry for correlated protein abundance-profiling we were able to identify a cluster of 82 candidate proteins that can be localized to the trypanosomal MOM with high confidence. This enabled us to identify a highly unusual, potentially archaic protein import machinery that might also transport tRNAs. Moreover, two-thirds of the identified polypeptides present on the MOM have never been associated with mitochondria before. 40 proteins share homology with proteins of known functions. The function of 42 proteins remains unknown. 11 proteins are essential for the disease-causing bloodstream form of T. brucei and therefore may be exploited as novel drug targets. A comparison with the outer membrane proteome of yeast defines a set of 17 common proteins that are likely present in the MOM of all eukaryotes. Known factors involved in the regulation of mitochondrial morphology are virtually absent in T. brucei. Interestingly, RNAi-mediated ablation of three outer membrane proteins of unknown function resulted in a collapse of the network-like mitochondrion of insect-stage parasites and therefore directly or indirectly are involved in the regulation of mitochondrial morphology.

Reflections on the Nature of Preferentialism in Services Trade

The Graduate Institute organized an academic workshop and roundtable on the occasion of EFTA's 50th Anniversary in Geneva under the chairmanship of H.E. Doris Leuthard, President of the Swiss Confederation. Pierre Sauve, Deputy Managing Director and Director of Studies, WTI and Co-leader, NCCR-Trade work programme on preferentialism and Anirudh Shingal, Senior Research Fellow, WTI and Co-leader, NCCR-Trade work programme on impact assessment of trade, co-authored a paper on the nature of preferentialism in services trade, which Anirudh presented at the workshop. The event was extremely well-attended by high profile dignitaries and academics including President Leuthard; Director General of the WTO, Pascal Lamy; trade ministers of Brazil and Finland; Jan Kubis, Executive Secretary of the UNECE and several current and former ambassadors. The academic workshop, moderated by Theresa Carpenter (Graduate Institute, Geneva), began in the morning with Prof. Victor Norman's (Norwegian School of Economics & Business Administration) presentation on the future of EFTA. Other presentations included those by Prof. Peter Egger (ETH Zurich) on the structural estimation of gravity models with market entry dynamics and by Prof. Richard Baldwin (Graduate Institute, Geneva) on 21st century regionalism. The high-profile Panel in the afternoon, moderated by Prof. Richard Baldwin, was led by President Leuthard who spoke on free trade agreements and the multilateral trading system in 2020. The keynote address at the Panel was delivered by Prof. Jagdish Bhagwati (Coulmbia University), who spoke on strengthening defences against protectionism and liberalizing trade.