Cologne Seminars on Ageing "Molecular mechanisms controlling lysosomal homeostasis and its roles in aging"

About Shuhei' s talk:

Lysosomes are the main digestive organelles and serve as a signaling hub linking environmental cues to cellular metabolism. Through these functions, lysosomes play a critical role in maintaining cellular and organismal homeostasis. However, how lysosomal homeostasis is maintained is not well understood. Lysosomes are frequently damaged by a variety of substances including crystals, silica, lipids, bacteria, toxins, amyloid proteins and ROS. When lysosomes are damaged, acidic contents leak out, which leads to oxidative stress, inflammation, and cell death, making the damaged lysosomes harmful to cells. To restore lysosomal function after damage, cells have developed several defense mechanisms collectively called “lysosomal damage response.” We and others have shown that the induction of damaged lysosome-targeting selective ‘macro’autophagy and the activation of TFEB, a master transcriptional regulator of lysosomal biogenesis, are part of the lysosomal damage response. In addition, we have recently revealed that lysosomes with small membrane ruptures are rapidly repaired by ‘micro’autophagy. Importantly, the failure of the response results in accelerated cellular senescence and organismal aging with an increase in damaged lysosomes, implying that the maintenance of lysosomal integrity by the lysosomal damaged response is critical to prevent aging.