Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury

I Maejima, A Takahashi, H Omori, T Kimura… - The EMBO …, 2013 - embopress.org
I Maejima, A Takahashi, H Omori, T Kimura, Y Takabatake, T Saitoh, A Yamamoto…
The EMBO journal, 2013embopress.org
Diverse causes, including pathogenic invasion or the uptake of mineral crystals such as
silica and monosodium urate (MSU), threaten cells with lysosomal rupture, which can lead to
oxidative stress, inflammation, and apoptosis or necrosis. Here, we demonstrate that
lysosomes are selectively sequestered by autophagy, when damaged by MSU, silica, or the
lysosomotropic reagent l‐Leucyl‐L‐leucine methyl ester (LLOMe). Autophagic machinery is
recruited only on damaged lysosomes, which are then engulfed by autophagosomes. In an …
Diverse causes, including pathogenic invasion or the uptake of mineral crystals such as silica and monosodium urate (MSU), threaten cells with lysosomal rupture, which can lead to oxidative stress, inflammation, and apoptosis or necrosis. Here, we demonstrate that lysosomes are selectively sequestered by autophagy, when damaged by MSU, silica, or the lysosomotropic reagent l‐Leucyl‐L‐leucine methyl ester (LLOMe). Autophagic machinery is recruited only on damaged lysosomes, which are then engulfed by autophagosomes. In an autophagy‐dependent manner, low pH and degradation capacity of damaged lysosomes are recovered. Under conditions of lysosomal damage, loss of autophagy causes inhibition of lysosomal biogenesis in vitro and deterioration of acute kidney injury in vivo. Thus, we propose that sequestration of damaged lysosomes by autophagy is indispensable for cellular and tissue homeostasis.
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