Browsing by Author "Mälkönen, Henriikka"

Background: Mitophagy eliminates damaged or defective mitochondria and maintains a healthy mitochondrial network, which is critical for cell and tissue function. In 2016, McWilliams et al. discovered a distinctive pattern of spatially restricted cellular clusters in the developing mouse heart, characterised by high levels of mitophagy. Since this discovery, these highly mitophagic zones have been extensively examined using conventional approaches, yet the identity of these cells and the physiological regulation and significance of developmental cardiomitophagy at this stage remain unclear. My project aimed to make a meaningful advance in defining cell subtypes in the developing heart, with the future goal of using this information to delineate the identity and properties of mitophagic cells in vivo. Methods: To address this longstanding challenge in the field, I established a new protocol to rigorously discriminate all cell subtypes in the heart without preselected markers, using a state-of-the-art contemporary method. Results: Following optimization, the protocol was successful with high reproducibility for both adult and embryonic heart tissue, and I was able to perform a definitive in vivo experiment in collaboration with a world class centre. My work defines the genetic identity of distinct cellular subtypes in the heart. Conclusions: My thesis work provides a solid launchpad for the future delineation of developing cardiac cells undergoing mitophagy in vivo. A rigorous and targeted investigation of developmental cardiomitophagy in the mammalian heart is now possible and underway as a consequence of this work.