Article
Biochemistry & Molecular Biology
Juncal Garcia-Garcia, Anne Kristin McLaren Berge, Katrine Stange Overa, Kenneth Bowitz Larsen, Zambarlal Bhujabal, Andreas Brech, Yakubu Princely Abudu, Trond Lamark, Terje Johansen, Eva Sjottem
Summary: TRIM27 is a multifunctional protein involved in various cellular functions. It has been found to facilitate mitochondrial clustering via SQSTM1/p62 and promote mitophagy by stabilizing phosphorylated TBK1 on mitochondria.
Review
Cell Biology
Jason P. Chua, Hortense De Calbiac, Edor Kabashi, Sami J. Barmada
Summary: Protein homeostasis mechanisms are crucial for maintaining the health of neurons and other cells in the central nervous system, while autophagy plays a key role in preventing and combating pathogenic insults that may lead to neurodegenerative diseases. However, the specific mechanisms underlying the neuroprotective role of autophagy, neuronal resistance to autophagy induction, and the effects of autophagy-impairing mutations on neurons are not fully understood. Additionally, the contribution of non-cell autonomous effects of autophagy dysfunction to ALS pathogenesis remains incompletely defined.
Article
Cell Biology
Inwoo Hwang, Byeong-Seong Kim, Ho Yun Lee, Sung-Woo Cho, Seung Eun Lee, Jee-Yin Ahn
Summary: Increased ubiquitination of PA2G4/EBP1 following cerebral ischemia-reperfusion injury promotes mitophagy induction and may be implicated in neuroprotection.
Review
Neurosciences
Yuval Gurfinkel, Nicole Polain, Krushna Sonar, Penelope Nice, Ricardo L. Mancera, Sarah Lyn Rea
Summary: Mutations in the TBK1 gene are associated with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), and different mutation types have been reported. Nonsense mutations cause haploinsufficiency, while the disease mechanisms of missense mutations are not fully understood. TBK1 functions in neuroinflammation and regulates autophagy pathways. Studies have investigated the effects of missense mutations on TBK1 substrates, TBK1 homodimerization, interaction with optineurin, and the regulation of autophagy and neuroinflammatory pathways.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Toshinaru Fukae, Takeshi Miyatsuka, Miwa Himuro, Yuka Wakabayashi, Hitoshi Iida, Shuhei Aoyama, Tomoya Mita, Fuki Ikeda, Hidenori Haruna, Noriyuki Takubo, Yuya Nishida, Toshiaki Shimizu, Hirotaka Watada
Summary: Autophagy plays a crucial role in intracellular quality control, while the accumulation of p62 under autophagy-deficient conditions has little effect on 0 cell function.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Olivia Harding, Chantell S. Evans, Junqiang Ye, Jonah Cheung, Tom Maniatis, Erika L. F. Holzbaur
Summary: TBK1, a multifunctional kinase, plays a crucial role in mitophagy and its mutations associated with ALS may contribute to disease pathogenesis by inducing mitochondrial stress or inhibiting mitophagic flux. Some TBK1 mutations have minimal impact on mitophagy, suggesting that cell-type specific effects, cumulative damage, or other TBK1-dependent pathways also play a role in the development of ALS.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Yinfeng Xu, Yaosen Wu, Lei Wang, Zhuo Ren, Lijiang Song, Hui Zhang, Chuying Qian, Qian Wang, Zhengfu He, Wei Wan
Summary: The study uncovered a regulatory role of autophagy in RNA metabolism, showing that autophagy-deficient cells have higher levels of 47S precursor rRNA due to accumulation of SQSTM1. This accumulation potentiates MTORC1 signaling, leading to increased rRNA transcription from rDNA and promoting protein synthesis and cell proliferation.
Article
Biochemistry & Molecular Biology
Tetsushi Kataura, Elsje G. Otten, Yoana Rabanal-Ruiz, Elias Adriaenssens, Francesca Urselli, Filippo Scialo, Lanyu Fan, Graham R. Smith, William M. Dawson, Xingxiang Chen, Wyatt W. Yue, Agnieszka K. Bronowska, Bernadette Carroll, Sascha Martens, Michael Lazarou, Viktor Korolchuk
Summary: Mitophagy is essential for maintaining cellular homeostasis. The best characterised pathway involves the stabilisation of PINK1 and recruitment of Parkin to damaged mitochondria. NDP52 recognises ubiquitinated mitochondrial proteins and initiates autophagic vesicle formation. This study found that oxidation of NDP52 is crucial for efficient PINK1/Parkin-dependent mitophagy, and proposed that redox sensing allows mitophagy to function as an oxidative stress response.
Review
Cell Biology
Xiaolan Fan, Tiantian Huang, Yingdong Tong, Ziqiang Fan, Ziyue Yang, Deying Yang, Xueping Mao, Mingyao Yang
Summary: p62, also known as SQSTM1, is a crucial predictor of autophagic flux and plays a role in maintaining protein homeostasis in cells. It has the ability to resist oxidative stress, and its multiple domains allow it to interact with vital signaling pathways, influencing cell proliferation, apoptosis, and survival. Recent studies have also shown its involvement in the aging process.
AGEING RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Yasukazu Takanezawa, Ryohei Harada, Yoshio Shibagaki, Yui Kashiwano, Ryosuke Nakamura, Yuka Ohshiro, Shimpei Uraguchi, Masako Kiyono
Summary: p62 interacts with NEDD4 to alleviate MeHg toxicity through the formation of a complex.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Jiafeng Chen, Zheng Gao, Xiaogang Li, Yinghong Shi, Zheng Tang, Weiren Liu, Xin Zhang, Ao Huang, Xuanming Luo, Qiang Gao, Guangyu Ding, Kang Song, Jian Zhou, Jia Fan, Xiutao Fu, Zhenbin Ding
Summary: The study indicates that abundant expression of p62 is associated with the malignant progression of ICC and could serve as a potential therapeutic target in antimetastatic strategies.
Article
Oncology
Sheng Wang, Wei Feng, Wulin Wang, Xiaoman Ye, Hao Chen, Chunzhao Yu
Summary: This study aims to increase the sensitivity of gemcitabine chemotherapy for pancreatic cancer by silencing the Girdin gene, showing that Girdin may enhance chemotherapy resistance to gemcitabine through regulating autophagy activity.
FRONTIERS IN ONCOLOGY
(2021)
Article
Food Science & Technology
Shangyun Lu, Jiali Xu, Yang Xu, Yang Liu, Dongxing Shi, Jia Wang, Fubin Qiu
Summary: Maintaining the integrity and stability of the gut tract is crucial for overall body health. This study focused on using autophagy to balance gut homeostasis and found that glycyrol (GC), a coumarin compound from Glycyrrhiza uralensis Fisch, can activate autophagy and attenuate colon injury. By inhibiting the interaction between SQSTM1/p62 and ubiquitin-specific protease 8 (USP8), GC promotes the ubiquitination of p62 and activates autophagy. These findings suggest that GC has potential as a novel colon protector and should be further investigated.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Article
Biochemistry & Molecular Biology
Guiomar Rodriguez-Perinan, Ana de la Encarnacion, Fermin Moreno, Adolfo Lopez de Munain, Ana Martinez, Angeles Martin-Requero, Carolina Alquezar, Fernando Bartolome
Summary: LOF mutations in GRN gene cause FTLD-TDP, and mitochondrial dysfunction is involved in the pathogenesis of PGRN deficiency-associated FTLD-TDP. PGRN deficiency induces mitochondrial depolarization, elevated ROS production, and reduced ATP levels. The accumulation of damaged mitochondria and autophagy dysfunction were observed in PGRN-deficient cells, which can be rescued by CK-1 delta inhibitors.
Article
Oncology
Fangqin Yu, Runsheng Ma, Chenguang Liu, Lele Zhang, Kaixiang Feng, Meiqi Wang, Detao Yin
Summary: The study investigated the effect of SQSTM1/p62 on papillary thyroid cancer (PTC) cells, finding that p62 expression was higher in tumor tissues compared to normal tissues. Knockout of p62 inhibited cell proliferation, cell cycle, and induced apoptosis in PTC cells. The AMPK/AKT/mTOR pathway was found to be involved in mediating these effects, suggesting p62 as a potential therapeutic target for PTC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sipin Zhu, Sarah L. Rea, Taksum Cheng, Hao Tian Feng, John P. Walsh, Thomas Ratajczak, Jennifer Tickner, Nathan Pavlos, Hua-Zi Xu, Jiake Xu
JOURNAL OF CELLULAR BIOCHEMISTRY
(2016)
Article
Multidisciplinary Sciences
Hua Ying, An Qin, Tak S. Cheng, Nathan J. Pavlos, Sarah Rea, Kerong Dai, Ming H. Zheng
Article
Neurosciences
Alice Goode, Sarah Rea, Melanie Sultana, Barry Shaw, Mark S. Searle, Robert Layfield
MOLECULAR AND CELLULAR NEUROSCIENCE
(2016)
Article
Cell Biology
Bryan K. Ward, Sarah L. Rea, Aaron L. Magno, Bernadette Pedersen, Suzanne J. Brown, Shelby Mullin, Ajanthy Arulpragasam, Evan Ingley, Arthur D. Conigrave, Thomas Ratajczak
JOURNAL OF CELLULAR PHYSIOLOGY
(2018)
Review
Oncology
Sarah L. Rea, Veronika Majcher, Mark S. Searle, Rob Layfield
EXPERIMENTAL CELL RESEARCH
(2014)
Article
Neurosciences
A. Foster, D. Scott, R. Layfield, S. L. Rea
MOLECULAR AND CELLULAR NEUROSCIENCE
(2019)
Review
Biochemistry & Molecular Biology
Sharmeelavathi Krishnan, Yasaswi Shrestha, Dona P. W. Jayatunga, Sarah Rea, Ralph Martins, Prashant Bharadwaj
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Biochemistry & Molecular Biology
Alistair Wood, Yuval Gurfinkel, Nicole Polain, Wesley Lamont, Sarah Lyn Rea
Summary: ALS and FTLD are neurodegenerative disorders with pathological, clinical, and genetic overlaps. The primary pathological protein, TDP-43, is observed in aggregates in affected tissues in majority of cases. Disease pathogenesis involves changes in RNA splicing, abnormal stress granules, mitochondrial dysfunction, and other cellular processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
A. D. Foster, L. L. Flynn, C. Cluning, F. Cheng, J. M. Davidson, A. Lee, N. Polain, R. Mejzini, N. Farrawell, J. J. Yerbury, R. Layfield, P. A. Akkari, S. L. Rea
Summary: The study found that overexpression of p62 leads to mislocalization of TDP-43 into cytoplasmic aggregates, aberrant TDP-43 cleavage, and neuronal death, potentially contributing to the pathogenesis of ALS and FTLD.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Melanie A. Sultana, Carmel Cluning, Wai-Sin Kwong, Nicole Polain, Nathan J. Pavlos, Thomas Ratajczak, John P. Walsh, Jiake Xu, Sarah L. Rea
Summary: Ajuba and SQSTM1/p62 play crucial roles in regulating NF-kappa B signaling, with SQSTM1/p62 protecting Ajuba from degradation by autophagy. This interaction impacts cellular functions and disease pathogenesis, highlighting the importance of SQSTM1/p62 in modulating Ajuba-mediated signaling pathways.
Review
Neurosciences
Yuval Gurfinkel, Nicole Polain, Krushna Sonar, Penelope Nice, Ricardo L. Mancera, Sarah Lyn Rea
Summary: Mutations in the TBK1 gene are associated with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), and different mutation types have been reported. Nonsense mutations cause haploinsufficiency, while the disease mechanisms of missense mutations are not fully understood. TBK1 functions in neuroinflammation and regulates autophagy pathways. Studies have investigated the effects of missense mutations on TBK1 substrates, TBK1 homodimerization, interaction with optineurin, and the regulation of autophagy and neuroinflammatory pathways.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Cell Biology
Adriana Delice Foster, Sarah Lyn Rea
NEURAL REGENERATION RESEARCH
(2020)
Article
Endocrinology & Metabolism
M. A. Sultana, N. J. Pavlos, Lynley Ward, J. P. Walsh, S. L. Rea
Article
Endocrinology & Metabolism
Cameron Britton, Suzanne Brown, Lynley Ward, Sarah L. Rea, Thomas Ratajczak, John P. Walsh
CALCIFIED TISSUE INTERNATIONAL
(2017)