Related Experiment Video
Updated: Aug 11, 2026
08:43
Simultaneous Measurement of Mitochondrial Calcium and Mitochondrial Membrane Potential in Live Cells by Fluorescent Microscopy
Published on: January 24, 2017
DRP1-mediated mitochondrial fragmentation is a druggable vulnerability in multiple myeloma
Maria Eugenia Gallo Cantafio1, Noemi Puccio2, Roberta Torcasio3
1University Magna Graecia of Catanzaro, Catanzaro, Italy.
Blood
|August 4, 2026
Summary
Mitochondrial fission drives multiple myeloma (MM) progression and drug resistance. Inhibiting the DRP1 protein, encoded by DNM1L, halts MM growth and induces cell death, offering a new therapeutic strategy for resistant MM.
Area of Science:
- Cellular Biology
- Cancer Research
- Mitochondrial Biology
Background:
- Mitochondrial dynamics are crucial for cellular homeostasis and cancer progression.
- The role of mitochondrial remodeling in multiple myeloma (MM) remains unclear.
- MM cells exhibit a fragmented mitochondrial network, especially when resistant to treatment.
Purpose of the Study:
- To investigate the functional relevance of mitochondrial remodeling in multiple myeloma.
- To explore the therapeutic potential of targeting mitochondrial fission in MM.
Main Methods:
- Ultrastructural analysis of MM cells.
- Transcriptomic profiling of patient-derived datasets.
- Genetic targeting of DNM1L and pharmacologic inhibition of DRP1 (using Drpitor1a).
- In vitro and in vivo studies in bortezomib-resistant xenograft models.
Main Results:
- MM cells show increased mitochondrial fragmentation and DNM1L/DRP1 upregulation, linked to poor survival.
- DNM1L targeting or DRP1 inhibition caused mitochondrial dysfunction, impaired oxidative phosphorylation, and potent anti-myeloma activity.
- Combined apoptosis and ferroptosis were observed, with c-MYC regulating DNM1L expression.
- DRP1 inhibition in vivo reversed resistance in a bortezomib-resistant model.
Conclusions:
- Aberrant mitochondrial fission is a key feature of multiple myeloma.
- DRP1 inhibition demonstrates significant anti-myeloma activity, particularly in relapsed/refractory MM.
- Targeting DRP1 represents a promising therapeutic strategy for multiple myeloma.
Related Concept Videos
01:10Drugs that Destabilize Microtubules
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
02:56Treatment Resistant Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...