The legacy of János Kovács: a lifelong devotion to advancing autophagy research

Hungarian scientist and a pioneer of autophagy research, emeritus professor János Kovács died in Budapest at the age of 92 on March 3, 2022. In this obituary, we introduce some of his contributions to the field of autophagy as researcher, group leader and our mentor during the past 60 years.

János Kovács summarized his remarkable career in an autobiography that was published 21 years ago when he officially retired [1]. We now would like to provide some examples of his influence on autophagy research in his remembrance. During most of his scientific carrier János Kovács studied autophagy, and he was still carrying out transmission electron microscopy until 2015 [2,3]. The home of his teaching and research activity was constantly Eötvös Loránd University in Budapest, Hungary, where he used to head the Department of General Zoology, the predecessor of the current Anatomy, Cell and Developmental Biology Department. He established the autophagy research community there that is still very much alive, with the third and fourth generations of researchers now working in this field.

From the early 1960s, the research interest of János Kovács focused on mildly injured cells from exocrine pancreas, liver, and seminal vesicle, in which a spectacular accumulation of the vital dye neutral red could be seen by light microscopy [4]. It was a great step forward when János Kovács managed to establish a laboratory of ultrastructural analysis at our university in the mid-1960s. Soon they identified huge numbers of dense bodies and many autophagic vacuoles in tissue samples of neutral red-injected mice using the transmission electron microscope [5]. He then chose autophagy as a long-term research project based on their accumulating results. At that time, the scarcity of publications on this topic clearly showed that it was not at all fashionable. However, regulation of this process and the formation of autophagosomes (referred to as initial autophagic vacuoles or AVi back then) was very interesting, even mysterious: invoking curiosity and thereby an ideal target for basic research.

János Kovács devised to tackle the subject from various angles:

1. Applying chemicals such as neutral red, vinblastine, leupeptin and chloroquine to interfere with the autophagic process (e.g., by altering the formation and/or maturation of autophagic vacuoles);

2. applying cell fractionation methods and isolating autophagic vacuoles at different stages of their maturation, with the hope to collect their bordering membranes for detailed characterization;

3. introducing in vitro methods to simplify experiments with mammalian cells;

4. introducing insects as a new model system.

To deal with the cell fractionation, the insect models, and the in vitro approaches, three freshly graduated master’s students: Gábor Réz, Miklós Sass, and Attila L. Kovács were recruited one by one to join his research group, respectively (note that Kovács is equivalent to the American Smith in Hungarian; Attila and János Kovács are not relatives). They achieved significant results and their talent and perseverance proved that János Kovács had the rare quality of choosing the right persons and keeping them as colleagues for a long time. He set a high standard, but those who worked under his leadership could feel safe, treated fairly and with empathy. In research he was most democratic: encouraging open discussions, accepting criticism, and supporting creativity.

In the 1970s and 1980s, important new results were achieved in the Kovács group, and more and more of these appeared in well-respected international journals thanks to the gradually easing political isolation of Hungary. New connections were established with foreign laboratories, and participation in international conferences became possible. From this period onwards, researchers from the Kovács lab have become significant participants of autophagy research activity worldwide. Publications focused on the effect of various drugs including vinblastine, leupeptin and chloroquine on autophagy in vivo [6–11], autophagy and its regulation in cabbage moth larvae [12–15], ultrastructural analyses of autophagic organelles in seminal vesicle cells in vitro [16,17], and subcellular fractionation of autophagic structures [18,19]. János Kovács even endorsed his colleagues to work independently in laboratories abroad, which was not trivial during the socialist era. International cooperation in the form of what is now called postdoctoral visits yielded important insights into the ultrastructure of autophagic structures by freeze-fracture electron microscopy in Italy [20], and comparative and quantitative studies on protein degradation and autophagy in the group of Per Seglen in Norway [21–24].

By the turn of the millennium, with the help and support of János Kovács, the three researchers of the second generation developed their own approaches and research groups, already with the help of young researchers of the third generation. These include studies of autophagy during carcinogenesis by Gábor Réz [25,26], and isolated pancreatic acini [27,28] and seminal vesicle epithelial cells where huge phagophores and autophagosomes could be induced [29] by Attila L. Kovács. The discovery of evolutionarily conserved autophagy genes in yeast necessitated the use of genetically accessible model organisms: Drosophila and Caenorhabditis, with the first papers published by the group of Miklós Sass [30] and Attila L. Kovács [31]. The work with Caenorhabditis was extended by cooperation with partners from various laboratories both within our university (Tibor Vellai) [32–34] and abroad (Hong Zhang) [35,36]. The initial Drosophila studies were also followed by significant findings published in leading international journals [37–39].

Despite the passing of the founder of our autophagy school, János Kovács, and the retirement of the three scientists belonging to the second era (Gábor Réz, Attila L. Kovács, and Miklós Sass), autophagy research is still thriving at our department. The research groups led by the third generation researchers (Gabor Juhasz [40–45] and Peter Low [46]), and emerging fourth generation group leaders who graduated from our department (Karolina Pircs [47], Péter Lőrincz [48], Szabolcs Takáts [49], and Tamás Csizmadia [50]) continue to reveal new secrets of autophagy and closely related processes.

The legacy of János Kovács makes our autophagy research school at Eötvös University, Budapest, Hungary a unique place, where ongoing work is based on six decades of continuously evolving experience and knowledge. A long-lasting influence like this is something that all of us would probably be happy to achieve.

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The author(s) reported there is no funding associated with the work featured in this article.