Discovering Mitokine Networks in Mammalian Models
Event details
| Date | 19.05.2016 |
| Hour | 15:00 › 16:00 |
| Speaker | Prof. Minho SHONG, M.D., Ph.D. Chungnam National University, South Korea |
| Location | |
| Category | Conferences - Seminars |
SEMINAR of the LAUSANNE INTEGRATIVE METABOLISM and NUTRITION ALLIANCE (LIMNA)
Abstract:
Recent in vivo studies in C. elegans and Drosophila revealed that UPRmt activation by inhibition of mitochondrial electron transport chain (ETC) functions increases lifespan (Houtkooper RH et al., Nature 2013; Durieux J et al., Cell 2011). This effect of ETC inhibition on longevity is modulated by cell-autonomous and cell-non-autonomous factors, known as mitokines, which may promote metabolic homeostasis. However, extrapolation of these studies into mammalian systems is extremely difficult because generalized impairment of ETC function in mice uniformly results in progressive deterioration of organ functions and premature death. To investigate whether the role of cell-non-autonomous mitokine networks is conserved in mammalian systems, we designed a spatio-temporal approach for gene expression and secretome analysis in mice with tissue-specific UPRmt activation.
Recently, we successfully generated and demonstrated relevant mouse models of tissue-specific UPRmt activation and ETC deficiency that are reminiscent of complex human disorders, e.g., neurodegeneration (Kim et al., Cell Metab, 2012), Parkinson’s disease, insulin resistance (Ryu et al., PLOS Genetics, 2013), and type 1 diabetes (Kim et al., Diabetologia, 2015). These models are based on tissue-specific knockout (KO) of Crif1, which encodes a factor required for biogenesis of ETC subunits. Loss of Crif1 resulted in abnormal proteostasis in the mitochondrial matrix and triggered the mitochondrial unfolded protein response (UPRmt).
Preliminary observations on phenotypes of tissue-specific Crif1-deficient mice revealed that Crif1-deficient cells and tissues express unique UPRmt activation e.g., adaptive transcriptomic changes and secretome responses (mitokines), which can be considered to be part of the phenomenon of “mitohormesis” (Yun J and Finkel T, Cell Metab, 2014). Based on these observations, we postulated that tissue-specific UPRmt and mitokine responses are critical cell-non-autonomous modifiers in disease progression, and that individual mitokines may act as disease markers and potential therapeutic targets in complex human disorders.
Bio:
Dr. Minho Song was born in Seoul, South Korea. He earned his B. S. degree in Applied Animal Science from Korea University in Seoul in 2003. He then migrated to the U. S. and earned his MS degree in swine nutrition under the guidance of Dr. Samuel Baidoo at the University of Minnesota in 2007. His Master's thesis was on the effects of distillers dried grains with soluble on performance, energy and nitrogen digestibility, and milk composition of lactating sows. After completion of his Master's degree, he joined the Animal Sciences Department at the University of Illinois and earned his Ph. D. degree in swine nutritional immunology and microbiology under the guidance of Dr. James Pettigrew in 2011. Dr. Song's Ph. D. and postdoctoral research focused on evaluations of feed ingredients as well as of dietary effects on pig health and productive performance, using nutritional, microbiological, and immunological approaches. From 2011 to 2012, he was a postdoctoral research associate in swine nutrition and physiology under the guidance of Dr. Hans Stein. In 2012, Dr. Song took a position as an assistant professor of nonruminant nutrition at Chungnam National University in Daejeon, South Korea.
Abstract:
Recent in vivo studies in C. elegans and Drosophila revealed that UPRmt activation by inhibition of mitochondrial electron transport chain (ETC) functions increases lifespan (Houtkooper RH et al., Nature 2013; Durieux J et al., Cell 2011). This effect of ETC inhibition on longevity is modulated by cell-autonomous and cell-non-autonomous factors, known as mitokines, which may promote metabolic homeostasis. However, extrapolation of these studies into mammalian systems is extremely difficult because generalized impairment of ETC function in mice uniformly results in progressive deterioration of organ functions and premature death. To investigate whether the role of cell-non-autonomous mitokine networks is conserved in mammalian systems, we designed a spatio-temporal approach for gene expression and secretome analysis in mice with tissue-specific UPRmt activation.
Recently, we successfully generated and demonstrated relevant mouse models of tissue-specific UPRmt activation and ETC deficiency that are reminiscent of complex human disorders, e.g., neurodegeneration (Kim et al., Cell Metab, 2012), Parkinson’s disease, insulin resistance (Ryu et al., PLOS Genetics, 2013), and type 1 diabetes (Kim et al., Diabetologia, 2015). These models are based on tissue-specific knockout (KO) of Crif1, which encodes a factor required for biogenesis of ETC subunits. Loss of Crif1 resulted in abnormal proteostasis in the mitochondrial matrix and triggered the mitochondrial unfolded protein response (UPRmt).
Preliminary observations on phenotypes of tissue-specific Crif1-deficient mice revealed that Crif1-deficient cells and tissues express unique UPRmt activation e.g., adaptive transcriptomic changes and secretome responses (mitokines), which can be considered to be part of the phenomenon of “mitohormesis” (Yun J and Finkel T, Cell Metab, 2014). Based on these observations, we postulated that tissue-specific UPRmt and mitokine responses are critical cell-non-autonomous modifiers in disease progression, and that individual mitokines may act as disease markers and potential therapeutic targets in complex human disorders.
Bio:
Dr. Minho Song was born in Seoul, South Korea. He earned his B. S. degree in Applied Animal Science from Korea University in Seoul in 2003. He then migrated to the U. S. and earned his MS degree in swine nutrition under the guidance of Dr. Samuel Baidoo at the University of Minnesota in 2007. His Master's thesis was on the effects of distillers dried grains with soluble on performance, energy and nitrogen digestibility, and milk composition of lactating sows. After completion of his Master's degree, he joined the Animal Sciences Department at the University of Illinois and earned his Ph. D. degree in swine nutritional immunology and microbiology under the guidance of Dr. James Pettigrew in 2011. Dr. Song's Ph. D. and postdoctoral research focused on evaluations of feed ingredients as well as of dietary effects on pig health and productive performance, using nutritional, microbiological, and immunological approaches. From 2011 to 2012, he was a postdoctoral research associate in swine nutrition and physiology under the guidance of Dr. Hans Stein. In 2012, Dr. Song took a position as an assistant professor of nonruminant nutrition at Chungnam National University in Daejeon, South Korea.
Practical information
- Informed public
- Free
Organizer
- Johan Auwerx for the Lausanne Integrative Metabolism and Nutrition Alliance (LIMNA)
Contact
- Johan Auwerx
IMPORTANT NOTICE: All external participants have to pass through SV Reception/Welcome Desk to be able to access to AI 1153. Contact person to call at arrival at SV Reception Desk: Johan Auwerx 30951 /Administrative Assistant: 39522.