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Called “bioblasts” in 1890, named “mitochondria” in 1898, baptized in 1957 as the “powerhouse of the cell” and christened in 1999 as the “motor of cell death”, mitochondria have been anointed in 2017 as “powerhouses of immunity”. In 1962, for the first time a causal link between mitochondria and human diseases was described, the genetic basis for which was revealed in 1988. The term “mitochondrial medicine” was coined in 1994. Research into mitochondria has been conducted ever since light microscopic studies during the end of the 19th century revealed their existence. To this day, new discoveries around this organelle and above all new insights into their fundamental role for human health and disease continue to surprise. Nowadays hardly any disease is known for which either the etiology or pathogenesis is not associated with malfunctioning mitochondria. In this second part of our review about recent developments in mitochondrial medicine we continue tracking and highlighting selected lines of mitochondrial research from their beginnings up to the present time. Mainly written for readers not familiar with this cell organelle, we hope both parts of our review will substantiate what we articulated over a decade ago, namely that the future of medicine will come through better understanding of the mitochondrion.

Research into elucidating structure and function of mitochondria has been quite steady between the time of discovery during the end of the 19th century until towards the late 1980’s. During the 1990s there was talk about a “comeback” of this organelle reflecting a widely revitalized interest into mitochondrial research which was based on two major discoveries made during that time. The first was the etiological association between human diseases and mitochondrial DNA mutations, while the second revealed the crucial function of mitochondria during apoptosis. The March 5th, 1999 issue of Science even featured a textbook image of a mitochondrion on its front cover and was entirely dedicated to this organelle. Whilst the term “comeback” might have been appropriate to describe the general excitement surrounding the new mitochondrial discoveries made during the 1990s, a term for describing the progress made in mitochondrial research during the last two decades is difficult to find. Between 2000 and 2020 the number of publications on mitochondria has skyrocketed. It is now widely accepted that there hardly exists any human disease for which either the etiology or pathogenesis does not seem to be associated with mitochondrial malfunction. In this review we will discuss and follow several lines of mitochondrial research from their early beginnings up to the present. We hope to be able to convince the reader of what we expressed about a decade ago, that the future of medicine will come through mitochondria.

Previously, we demonstrated that ferulate ethyl and tocopherol reduced HIV replication. In this study, we investigate whether the conjugation of both compounds (O-tocopheryl succinyl O-ethyl ferulate) can increase HIV inhibition. We show here for the first time that O-tocopheryl succinyl O-ethyl ferulate inhibits 80% of HIV replication (HIV-1 acute infection and HIV transmission), inhibits cell lipoperoxidation and prevents cellular glutathione consumption. Compared to ferulate ethyl and tocopheryl succinyl, O-tocopheryl succinyl O-ethyl ferulate inhibits more HIV replication. This may be due in part to the great increase in the lipophilicity of this compound.