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PERK-ATAD3A interaction provides a subcellular safe haven for protein synthesis during ER stress
Karinder K Brar1,2, Daniel T Hughes2, Jordan L Morris3
1Altos Labs, Cambridge Institute of Science, Granta Park, Cambridge CB21 6GP, UK.
Science (New York, N.Y.)
|August 8, 2024
Summary
During endoplasmic reticulum (ER) stress, mitochondrial translation is protected. The protein ATAD3A interacts with PERK to shield mitochondrial protein synthesis from widespread repression.
Area of Science:
- Cellular Biology
- Molecular Biology
- Stress Response
Background:
- Endoplasmic reticulum (ER) stress globally inhibits protein synthesis.
- Understanding localized stress effects on translation is challenging.
- Mitochondrial protein synthesis regulation during ER stress is unclear.
Purpose of the Study:
- To investigate how localized ER stress impacts subcellular translation rates.
- To identify mechanisms protecting mitochondrial translation during ER stress.
- To explore the role of ATAD3A in ER stress response.
Main Methods:
- Live-cell imaging of reporter mRNA translation.
- Co-immunoprecipitation to study protein interactions.
- Analysis of mitochondria-ER contact sites.
Main Results:
- Mitochondrial translation is unexpectedly protected during ER stress.
- ATAD3A interacts with PERK, competing for eIF2 binding.
- PERK-ATAD3A interactions increase, forming mitochondria-ER contacts and attenuating PERK signaling.
Conclusions:
- ATAD3A mediates protection of mitochondrial translation during ER stress.
- PERK-ATAD3A interactions control subcellular translational repression.
- This mechanism mitigates ER stress impact on mitochondrial protein expression.
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