Tom70-based transcriptional regulation of mitochondrial biogenesis and aging
- Buck Institute for Research on Aging, United States
- National University of Singapore, Singapore
Abstract
Mitochondrial biogenesis has two major steps: the transcriptional activation of nuclear genome-encoded mitochondrial proteins and the import of nascent mitochondrial proteins that are synthesized in the cytosol. These nascent mitochondrial proteins are aggregation-prone and can cause cytosolic proteostasis stress. The transcription factor-dependent transcriptional regulations and the TOM-TIM complex-dependent import of nascent mitochondrial proteins have been extensively studied. Yet, little is known regarding how these two steps of mitochondrial biogenesis coordinate with each other to avoid the cytosolic accumulation of these aggregation-prone nascent mitochondrial proteins. Here we show that in budding yeast, Tom70, a conserved receptor of the TOM complex, moonlights to regulate the transcriptional activity of mitochondrial proteins. Tom70's transcription regulatory role is conserved in Drosophila. The dual roles of Tom70 in both transcription/biogenesis and import of mitochondrial proteins allow the cells to accomplish mitochondrial biogenesis without compromising cytosolic proteostasis. The age-related reduction of Tom70, caused by reduced biogenesis and increased degradation of Tom70, is associated with the loss of mitochondrial membrane potential, mtDNA, and mitochondrial proteins. While loss of Tom70 accelerates aging and age-related mitochondrial defects, overexpressing TOM70 delays these mitochondrial dysfunctions and extends the replicative lifespan. Our results reveal unexpected roles of Tom70 in mitochondrial biogenesis and aging.
Data availability
The published article includes all datasets generated or analyzed during this study. All original raw data can be accessed in Dryad Digital Repository, doi:10.5061/dryad.d7wm37q2n
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Tom70-based transcriptional regulation of mitochondrial biogenesis and agingDryad Digital Repository, doi:10.5061/dryad.d7wm37q2n.
Article and author information
Author details
Funding
Glenn Foundation for Medical Research (Glenn postdoctoral fellowship)
- Qingqing Liu
NIH Office of the Director (DP5OD024598)
- Chuankai Zhou
national institute on aging (R01 AG058742)
- Brian K Kennedy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Tom70-based transcriptional regulation of mitochondrial biogenesis and aging
eLife 11:e75658.
https://doi.org/10.7554/eLife.75658
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