| Budget Amount *help |
¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
Fiscal Year 2019: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2018: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Outline of Final Research Achievements |
Sensing and clearance of dysfunctional lysosomes is critical for cellular homeostasis. Here, we found that during the lysosomal damage response, Transcription factor EB (TFEB), a master transcriptional regulator of lysosomal biogenesis and autophagy, was activated dependent upon the non-canonical LC3 function. Furthermore, we demonstrated the presence and importance of this TFEB activation mechanism in kidneys in a mouse model of oxalate nephropathy accompanying lysosomal damage. A proximal tubule specific TFEB-knockout mouse exhibited progression of kidney injury induced by oxalate crystals. Together, our results revealed novel and unexpected mechanisms of TFEB activation by LC3 and their physiological relevance during the lysosomal damage response.
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