Conveying the legacy of Britton Chance in Northern Finland
Ilmo Hassinen / University of Oulo, Finland
15 April 2011
My postdoctoral stay in Johnson Foundation with Britton Chance was seminal for my subsequent career in biomedicine. In 1966 I had finished my doctoral thesis about hydrogen transfer into mitochondria during ethanol metabolism. It was logical to search for a postdoctoral position in a mitochondriology laboratory. Nils-Erik Leo Saris, the official opponent at the public defence of my thesis, was the first Finn having worked at Johnson Foundation and a suitable link to the University of Pennsylvania. So, I arrived in Philadelphia in April 1967.
My previous work had a bearing on Complex I, so that it was logical that I continued with the same subject of study also at the Johnson Foundation. Complex I was in those days a hot topic, since Britton Chance and collaborators had just published two papers about a chain of two flavins in Complex I. My subsequent experiments, however, showed that everything was not as it appeared. I showed that no flavin chain existed in Complex I, just one FMN. I was able to identify the other flavin, but it was in the soluble mitochondrial matrix. Those findings were the basis of the only paper I published during my Philadelphian stay (Hassinen & Chance: Biochim Biophys Res Commun 31: 895, 1968), but its importance for me was somewhere else.
My experimentation in Britton Chance's laboratory familiarized me with the methods of physical biochemistry, spectroscopy, optics and electronics, and because of my medical background I was interested in applying those at the level of intact tissues and organs. Crucial for subsequent developments was the 1968 summer course "Electronics for Scientist", arranged at the Johnson Foundation. Teachers were Joseph Higgins and John Leigh, from whom we learned the essence of analogue electronics, building amplifiers, etc. Even the economics of the course was clever: At registration, the participants had to make a deposition, and if they quitted or did not pass the examination, they lost the money and those who passed, divided the funds.
After my return back home to the Department of Medical Chemistry, University of Helsinki, I was eager to start with mitochondria. I desperately needed a sensitive dual wavelength spectrophotometer, but the Departmental funds were not sufficient for the purchase. So I made the bold decision to build the instrument on the basis of skills I learned in the Britton Chance laboratory. This was a lucky move, because the custom-built instrument was easy to adapt to various needs, when we turned towards optical readout of intact organs. Sufficient novelty was contained in further developments of the instrument to deserve publication (Hassinen & Jämsä: Anal Biochem 120:365, 1982: Hassinen: Meth Enzymol 123H: 311, 1986). The instrument is still in use in our laboratory.
The "mitochondria in situ" strategy has been one line of approaches in our studies on metabolic regulation and oxidative phosphorylation. After my move in 1973 to the University of Oulu in Northern Finland we adapted the isolated perfused heart as a versatile and practical platform where ATP consumption can be easily varied and its effects on energy metabolism studied by means of optical methods. Both surface optical and NMR spectroscopy (31P and 13C) have been applied.
The centre of effort in our studies has during the last 15 years been shifted to molecular biology, mitochondrial DNA, probing of mitochondrial complex I function and disease by site-directed mutagenesis in Escherichia coli NDH-1, but as depicted in our recent mutagenesis work (Maliniemi, Kervinen, Hassinen: Mitochondrion 9:394, 2009), readiness in spectroscopy I gathered in my early postdoctoral years at the University of Pennsylvania has been of enormous help.
After my postdoctoral period I have returned to the Chance laboratory for shorter periods. Six weeks in 1989 produced two publications in collaboration with Shoko Nioka, Kinji Ito and Britton Chance.
If applications of a variety of non-destructive monitoring methods (optical, absorbance, fluorescence and NMR spectroscopy) are taken as a criterion to present the legacy of Britton Chance since I first learned those in his laboratory, that tradition has contributed to at least sixteen of the Ph.D. thesis works from our group. For the same reason, 46 papers of my 176 research rapports on mitochondria can be regarded as continuation of the legacy of Britton Chance. Eight of the former members of our group are now in the rank of professors, so that the scientific family three is growing branches.
– Ilmo Hassinen
Professor Emeritus, Department of Medical Biochemistry and Molecular Biology
Institute of Biomedicine, University of Oulu, Finland
Representative papers in legacy of Britton Chance:
- Hassinen I, Hiltunen K (1975) Respiratory control in isolated perfused rat heart; Role of the equilibrium reactions between the mitochondrial electron carriers and the adenylate system. Biochim. Biophys. Acta 408:319-330
- Kauppinen RA, Hassinen IE (1984) Monitoring of mitochondrial membrane potential in isolated perfused rat heart. Am J Physiol. 247:H508-516.
- Vuorinen K, Ylitalo K, Peuhkurinen K, Raatikainen P, Ala-Rämi A, Hassinen IE. (1995) Mechanisms of ischemic preconditioning in rat myocardium. Roles of adenosine, cellular energy state, and mitochondrial F1F0-ATPase. Circulation 91:2810-2818.
- Ylitalo KV, Ala-Rämi A, Liimatta EV, Peuhkurinen KJ, Hassinen IE (2000) Intracellular free calcium and mitochondrial membrane potential in ischemia/reperfusion and preconditioning. J Mol Cell Cardiol 32:1223-1238.
- Liimatta EV, Gödecke A, Schrader J, Hassinen IE (2004) Regulation of cellular respiration in myoglobin-deficient mouse heart. Mol Cell Biochem 256-257:201-208
- Ala-Rämi A, Ylihautala M, Ingman P, Hassinen IE (2005) Influence of calcium-induced workload transitions and fatty acid supply on myocardial substrate selection. Metabolism 54:410-420.
- Liimatta E, Kantola AM, Hassinen IE (2007) Dual probe fluorescence monitoring of intracellular free calcium during ischemia in mouse heart by using continuous compensation for pH dependence of the dissociation constant of Fura-2, and the interference of myoglobin. J Biochem Biophys Methods 70:547-554.
- Karpanen T, Bry M, Ollila HM, Seppänen-Laakso T, Liimatta E, Leskinen H, Kivelä R, Helkamaa T, Merentie M, Jeltsch M, Paavonen K, Andersson LC, Mervaala E, Hassinen IE, Ylä-Herttuala S, Oresic M, Alitalo K (2008) Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy. Circ Res 103:1018-1026.
- Maliniemi P, Kervinen M, Hassinen IE (2009) Modeling of human pathogenic mutations in Escherichia coli complex I reveals a sensitive region in the fourth inside loop of NuoH. Mitochondrion 9:394-401.