ArticleThe EMBO journal2008
Proteolysis of AKAP121 regulates mitochondrial activity during cellular hypoxia and brain ischaemia.
Article in The EMBO journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 94 citations in OpenAlex.
- A-kinase anchoring protein 1: an independent predictor of coronary artery disease.BMC cardiovascular disorders · 2025Article
- The E3-ligase Siah2 activates mitochondrial quality control in neurons to maintain energy metabolism during ischemic brain tolerance.Cell death & disease · 2025Article
- SIAH3 is frequently epigenetically silenced in cancer and regulates mitochondrial metabolism.International journal of cancer · 2025Article
- Exploring the impact of circRNAs on cancer glycolysis: Insights into tumor progression and therapeutic strategies.Non-coding RNA research · 2024Review
- Ubiquitous regulation of cerebrovascular diseases by ubiquitin-modifying enzymes.Clinical and translational medicine · 2024Review
- TMEM135 links peroxisomes to the regulation of brown fat mitochondrial fission and energy homeostasis.Nature communications · 2023Article
- A Comprehensive Insight and Mechanistic Understanding of the Lipidomic Alterations Associated With DCM.JACC. Asia · 2023Review
- Review
- Brain Energy Metabolism in Ischemic Stroke: Effects of Smoking and Diabetes.International journal of molecular sciences · 2022Review
- Mitochondrial a Kinase Anchor Proteins in Cardiovascular Health and Disease: A Review Article on Behalf of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology.International journal of molecular sciences · 2022Review
- Siah2-GRP78 interaction regulates ROS and provides a proliferative advantage to Helicobacter pylori-infected gastric epithelial cancer cells.Cellular and molecular life sciences : CMLS · 2022Article
- The Role of Mitochondrial Dynamin in Stroke.Oxidative medicine and cellular longevity · 2022Review
- Mitochondrial ProteinFrontiers in pharmacology · 2022Article
- Regulation of neuronal bioenergetics as a therapeutic strategy in neurodegenerative diseases.Neural regeneration research · 2021Article
- E3 ubiquitin ligase-mediated regulation of vertebrate ocular development; new insights into the function of SIAH enzymes.Biochemical Society transactions · 2021Review
- Mitochondria as a therapeutic target for cardiac ischemia‑reperfusion injury (Review).International journal of molecular medicine · 2021Review
- Hypoxia-induced circular RNA hsa_circ_0008450 accelerates hepatocellular cancer progression via the miR-431/AKAP1 axis.Oncology letters · 2020Article
- Hypoxia and the hypoxia inducible factor 1α activate protein kinase A by repressing RII beta subunit transcription.Oncogene · 2020Article
- Knocking-out the Siah2 E3 ubiquitin ligase prevents mitochondrial NCX3 degradation, regulates mitochondrial fission and fusion, and restores mitochondrial function in hypoxic neurons.Cell communication and signaling : CCS · 2020Article
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A-kinase anchor protein 121 (AKAP121) assembles a multivalent signalling complex on the outer mitochondrial membrane that controls persistence and amplitude of cAMP and src signalling to mitochondria, and plays an essential role in oxidative metabolism and cell survival. Here, we show that AKAP121 levels are regulated post-translationally by the ubiquitin/proteasome pathway. Seven In-Absentia Homolog 2 (Siah2), an E3-ubiquitin ligase whose expression is induced in hypoxic conditions, formed a complex and degraded AKAP121. In addition, we show that overexpression of Siah2 or oxygen and glucose deprivation (OGD) promotes Siah2-mediated ubiquitination and proteolysis of AKAP121. Upregulation of Siah2, by modulation of the cellular levels of AKAP121, significantly affects mitochondrial activity assessed as mitochondrial membrane potential and oxidative capacity. Also during cerebral ischaemia, AKAP121 is degraded in a Siah2-dependent manner. These findings reveal a novel mechanism of attenuation of cAMP/PKA signaling, which occurs at the distal sites of signal generation mediated by proteolysis of an AKAP scaffold protein. By regulating the stability of AKAP121-signalling complex at mitochondria, cells efficiently and rapidly adapt oxidative metabolism to fluctuations in oxygen availability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.