Druggability of Mitochondrial Proteases: Emerging Targets and Therapeutic Opportunities in Cancer and Neurodegeneration
A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".
Deadline for manuscript submissions: 20 December 2026 | Viewed by 262
Special Issue Editors
Interests: medicinal chemistry; cancer; anticancer agents; drug screening; in vitro studies
Special Issues, Collections and Topics in MDPI journals
Interests: structure–activity relationships and druggability of mitochondrial quality-control proteins; medicinal chemistry strategies targeting mitochondrial proteostasis
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
Mitochondria are central hubs for cellular homeostasis, integrating energy production, apoptotic signaling, metabolic rewiring and oxidative stress responses. In recent years, an increasing body of evidence has highlighted mitochondrial rewiring and oxidative stress. Increasing evidence indicates that mitochondrial proteostasis processes, including mitoproteases chaperone systems, mitochondrial unfolded protein response (UPRmt) signaling and mitophagy pathways, have a critical role in determining cancer cell survival. Dysregulation of this interconnected protein quality control network is now recognized as a hallmark of both cancer progression and neurodegenerative disorders.
In cancer, aberrant regulation of mitochondrial proteases (e.g., LonP1, ClpP, …), adaptive metabolic remodeling under stress conditions and enhanced resistance to apoptosis confer selective survival advantages. These vulnerabilities highlight mitochondrial protein quality control as a druggable system, enabling novel therapeutic strategies based on the targeted modulation of key proteostasic nodes. Conversely, in neurodegenerative diseases, defective mitochondrial protein turnover and impaired organelle clearance and chronic activation of stress pathways contribute to mitochondrial and neuronal damage and disease progression, underscoring the need for precise pharmacological intervention.
This Special Issue aims to bring together cutting-edge research and reviews that critically examine the druggability of mitochondrial proteostasis processes, with a focus on the identification and validation of molecular targets, the development of chemical modulators and their therapeutic potential in oncology and neurodegeneration. Contributions bridging chemical biology, medicinal chemistry, pharmacology and translational research are particularly encouraged.
We welcome submissions including, but not limited to:
- Mitochondrial Proteases and Chaperones as druggable targets
- Mitochondrial Stress signaling and UPRmt modulation
- Proteostasis networks in cancer and neurodegenerative diseases
- Drug Discovery and Chemical Biology approaches
- Translational and therapeutic perspectives.
Dr. Morena Miciaccia
Dr. Maria Grazia Perrone
Guest Editors
Manuscript Submission Information
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Keywords
- mitochondrial proteostasis
- druggability
- mitochondrial proteases
- UPRmt signaling
- small-molecule modulators
- medicinal chemistry
- cancer therapy
- neurodegenerative diseases
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