Dynamin-Related Protein 1 at the Crossroads of Cancer

Abstract

Mitochondrial dynamics are known to have an important role in so-called age-related diseases, including cancer. Mitochondria is an organelle involved in many key cellular functions and responds to physiologic or stress stimuli by adapting its structure and function. Perhaps the most important structural changes involve mitochondrial dynamics (fission and fusion), which occur in normal cells as well as in cells under dysregulation, such as cancer cells. Dynamin-related protein 1 (DRP1), a member of the dynamin family of guanosine triphosphatases (GTPases), is the key component of mitochondrial fission machinery. Dynamin-related protein 1 is associated with different cell processes such as apoptosis, mitochondrial biogenesis, mitophagy, metabolism, and cell proliferation, differentiation, and transformation. The role of DRP1 in tumorigenesis may seem to be paradoxical, since mitochondrial fission is a key mediator of two very different processes, cellular apoptosis and cell mitosis. Dynamin-related protein 1 has been associated with the development of distinct human cancers, including changes in mitochondrial energetics and cellular metabolism, cell proliferation, and stem cell maintenance, invasion, and promotion of metastases. However, the underlying mechanism for this association is still being explored. Herein, we review the published knowledge on the role of DRP1 in cancer, exploring its interaction with different biological processes in the tumorigenesis context.

Human antiviral protein MxA forms novel metastable membrane-less cytoplasmic condensates exhibiting rapid reversible “crowding”-driven phase transitions

“…1D). This MxA reticulum was distinct from the punctate distribution of DLP1/DRP1, another large dynamin-family GTPase which associates with mitochondria (32, 33) (Fig. 1D).…”

“…Rabbit pAb to human MxA (also referred to as human Mx1) (H-285) (sc-50509), goat pAb to RTN4/NogoB (N18) (sc-11027) and mouse mAbs to cGAS (D-9)(sc-515777), β-tubulin (2-28-33) (sc-23949) and vimentin (V9) (sc-6260) were purchased from Santa Cruz Biotechnology Inc. (Santa Cruz, CA). Rabbit pAbs to atlastin 3 (ATL3) (ab104262) and to giantin (1-469 fragment) (ab24586) were purchased from Abcam Inc. (Cambridge, MA).…”

Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage inC. elegans

“…FZO-1 is required for proper fusion of the mitochondrial outer membrane while EAT-3/OPA1 regulates inner membrane fusion. In opposition to the activities of FZO-1 and EAT-3, DRP-1 is required for mitochondrial fission (Lima et al; Smirnova, Griparic, Shurland, & van der Bliek). The balance of this fusion and fission machinery in the upkeep of mitochondrial homeostasis allows cells to respond to changes in metabolic needs and external stress (Shaw & Nunnari; van der Bliek, Sedensky, & Morgan).…”

Adenosine 5'‐monophosphate‐activated protein kinase‐dependent mTOR pathway is involved in flavokawain B‐induced autophagy in thyroid cancer cells

“…However, the role of mitochondrial fission appears to change according to cell type. [32][33][34] It could be either FKB-induced mitochondrial injury or cancer cell protective changes facing energy stress. Cell-specific function of mitochondrial dynamics in different metabolic states therefore needs to be further explored.…”