Eukaryotic cells contain various organelles, such as mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosomes. However, all these organelles are degraded and lost during the terminal differentiation process of lens cells. This global organelle degradation has been known for more than 100 years, but its molecular mechanism and significance have remained unknown for a long time. We performed analyses using zebrafish and mice. The results showed that the global organelle degradation in the lens cells was not caused by autophagy involved in organelle degradation in normal cells but by phospholipase A/acyltransferase (PLAAT) family proteins in the cytosol and that the PLAAT-mediated organelle degradation was essential for lens transparency. Furthermore, we observed that PLAAT selectively degraded damaged organelles and that the physiological appearance of damaged organelles in the lens cells was dependent on the heat shock transcription factor HSF4, the causative gene product of human hereditary cataracts. In addition to elucidating the basic principle of lens transparency, this is the first study to discern the organelle degradation mechanism independent of autophagy.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 127: 1050-1054, 2023.