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SQSTM1/p62 Controls mtDNA Expression and Participates in Mitochondrial Energetic Adaption Via MRPL12

40 Pages Posted: 23 Apr 2020 Sneak Peek Status: Review Complete

See all articles by Wei Xin

Wei Xin

Shandong First Medical University - Shandong Provincial Hospital

Yuan Ma

Shandong University - Department of Endocrinology

Tingting Lv

Shandong University - Department of Endocrinology

Xia Gu

Shandong University - Department of Endocrinology

Suwei Zhu

Shandong University - Department of Endocrinology

Hong Feng

Shandong University

Junhui Zhen

Shandong University

Qiang Wan

Shandong University - Department of Endocrinology

More...

Abstract

Mitochondrial DNA (mtDNA) encodes thirteen core components of OXPHOS complexes and its steady expression is crucial for cellular energy homeostasis. However, the regulation of mtDNA expression machinery, along with its sensing mechanism to energetic stresses, is not fully understood. Here, we identified SQSTM1/p62 as an important regulator of mtDNA expression machinery, which could effectively induce mtDNA expression and the effects were mediated by p38-dependent upregulation of mitochondrial ribosomal protein L12 (MRPL12) in renal tubular epithelial cells (TECs), a highly energy-demanding cell type with energy supply relying heavily on OXPHOS. We further identified a direct binding site within the MRPL12 promoter to ATF2, the downstream effector of p38. Besides, SQSTM1/p62-induced mtDNA expression is involved in both serum deprivation and hypoxia induced mitochondrial response, which was further highlighted by kidney injury phenotype of TECs-specific SQSTM1/p62 knockout mice. Collectively, these data suggest that SQSTM1/p62 is a key regulator and energetic sensor of mtDNA expression machinery.

Suggested Citation

Xin, Wei and Ma, Yuan and Lv, Tingting and Gu, Xia and Zhu, Suwei and Feng, Hong and Zhen, Junhui and Wan, Qiang, SQSTM1/p62 Controls mtDNA Expression and Participates in Mitochondrial Energetic Adaption Via MRPL12. Available at SSRN: https://ssrn.com/abstract=3575117 or http://dx.doi.org/10.2139/ssrn.3575117
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Wei Xin

Shandong First Medical University - Shandong Provincial Hospital ( email )

Jinan
China

Yuan Ma

Shandong University - Department of Endocrinology

China

Tingting Lv

Shandong University - Department of Endocrinology ( email )

China

Xia Gu

Shandong University - Department of Endocrinology

China

Suwei Zhu

Shandong University - Department of Endocrinology ( email )

China

Hong Feng

Shandong University

27 Shanda Nanlu
South Rd.
Jinan, Shandong 250100
China

Junhui Zhen

Shandong University ( email )

27 Shanda Nanlu
South Rd.
Jinan, Shandong 250100
China

Qiang Wan (Contact Author)

Shandong University - Department of Endocrinology ( email )

China

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