Investigating the role of an Hsp40 molecular chaperone in and beyond ER quality control (2012)

Undergraduate: Jaclyn Bonner

Faculty Advisor: Doug Cyr
Department: Chemistry

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Accumulation of misfolded proteins can disrupt cellular protein homeostasis, causing cell stress that often results in disease states. The cell has developed numerous quality control mechanisms to prevent this, where molecular chaperones refold, degrade, or sequester misfolded proteins. Molecular chaperones are capable of acting in modular complexes whereby a single chaperone can have several different functions in quality control depending on its interaction partners. A novel Hsp40 co-chaperone was identified in a complex in the ER membrane that facilitates degradation of a large transmembrane ion channel. From a screen to identify other potential interaction partners and substrates of this Hsp40, a number of potential substrates were surprisingly found to be localized to mitochondria. This unexpected result can be logically resolved by the fact that we have verified substrates of this co-chaperone involved in calcium signaling, and that the ER and mitochondria are physically linked at sites of calcium transfer. Thus we hypothesize that our Hsp40 is involved in linking ER and mitochondria functions through calcium signaling between the two organelles.