# Is mitochondrial fragmentation (drp1) more likely to be good than mitochondrial fusion (opa1) ? Does damaging mitochondria to an extent increase selection pressure? **URL:** \ **Category:** General\ **Created:** [April 24, 2024, 12:20am UTC](https://www.rapamycin.news/t/is-mitochondrial-fragmentation-drp1-more-likely-to-be-good-than-mitochondrial-fusion-opa1-does-damaging-mitochondria-to-an-extent-increase-selection-pressure/13535 "2024-04-24T00:20:43Z")\ **Posts on this page:** 6\ **Page:** 1
**Author:** ![AlexKChen](https://www.rapamycin.news/user_avatar/www.rapamycin.news/alexkchen/32/385_2.png) [@AlexKChen](https://www.rapamycin.news/u/AlexKChen)\ **Post date:** [April 24, 2024, 12:20am UTC](https://www.rapamycin.news/t/is-mitochondrial-fragmentation-drp1-more-likely-to-be-good-than-mitochondrial-fusion-opa1-does-damaging-mitochondria-to-an-extent-increase-selection-pressure/13535/1 "2024-04-24T00:20:43Z")
At least when mitochondria fragment, they get phagocytosed more easily Doesn’t this happen more often with exercise, fasting, or starvation? Sometimes if the division is asymmetrical, the one with more damaged parts can get degraded I saw a paper showing that preventing mitochondrial damage is not always a good thing (detrimental effects). Mitochondria have a life of their own - dynamics VERY different from most other cell parts and operate more like bacteria where evolutionary pressures can make the more robust ones crowd out the less robust ones if you increase selection pressure - and mitodamage IS a selection pressure * * * Another paper [https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(24)00031-8?\_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0968000424000318%3Fshowall%3Dtrue](https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(24)00031-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0968000424000318%3Fshowall%3Dtrue) ---
**Author:** ![John\_Hemming](https://www.rapamycin.news/user_avatar/www.rapamycin.news/john_hemming/32/6542_2.png) [@John\_Hemming](https://www.rapamycin.news/u/John_Hemming)\ **Post date:** [April 24, 2024, 2:47am UTC](https://www.rapamycin.news/t/is-mitochondrial-fragmentation-drp1-more-likely-to-be-good-than-mitochondrial-fusion-opa1-does-damaging-mitochondria-to-an-extent-increase-selection-pressure/13535/2 "2024-04-24T02:47:53Z")
Do you have a link to this paper. I would think protecting mtDNA was good. ---
**Author:** ![AlexKChen](https://www.rapamycin.news/user_avatar/www.rapamycin.news/alexkchen/32/385_2.png) [@AlexKChen](https://www.rapamycin.news/u/AlexKChen)\ **Post date:** [April 28, 2024, 7:30am UTC](https://www.rapamycin.news/t/is-mitochondrial-fragmentation-drp1-more-likely-to-be-good-than-mitochondrial-fusion-opa1-does-damaging-mitochondria-to-an-extent-increase-selection-pressure/13535/3 "2024-04-28T07:30:47Z")
Lymecycline induces mitostress and is pro longevity ---
**Author:** ![AlexKChen](https://www.rapamycin.news/user_avatar/www.rapamycin.news/alexkchen/32/385_2.png) [@AlexKChen](https://www.rapamycin.news/u/AlexKChen)\ **Post date:** [July 21, 2024, 4:46am UTC](https://www.rapamycin.news/t/is-mitochondrial-fragmentation-drp1-more-likely-to-be-good-than-mitochondrial-fusion-opa1-does-damaging-mitochondria-to-an-extent-increase-selection-pressure/13535/4 "2024-07-21T04:46:52Z")
Not due to selection pressure, but due to stress signalling. > **[Cells Across the Body Talk to Each Other About Aging](https://nautil.us/cells-across-the-body-talk-to-each-other-about-aging-494209/?utm_source=tw-naut&utm_medium=organic-social)** > > When mitochondria stop communicating, the biological clock starts winding down. ---
**Author:** ![AlexKChen](https://www.rapamycin.news/user_avatar/www.rapamycin.news/alexkchen/32/385_2.png) [@AlexKChen](https://www.rapamycin.news/u/AlexKChen)\ **Post date:** [July 22, 2025, 6:43pm UTC](https://www.rapamycin.news/t/is-mitochondrial-fragmentation-drp1-more-likely-to-be-good-than-mitochondrial-fusion-opa1-does-damaging-mitochondria-to-an-extent-increase-selection-pressure/13535/5 "2025-07-22T18:43:00Z")
Exercise/PGC1alpha increase mitofission right? CR increases mitofission right? Parkin does, right? the relationship is NOT always clearcut In essence, what the authors did in dFBNs (the glutamatergic “sleep‑control” neurons that project to the dorsal fan‑shaped body in Drosophila) was to take the core fusion/fission machinery—Drp1 (fission), Marf (mitofusin), and Opa1 (inner‑membrane fusion)—and push it one way or the other: 1. **Driving fission (↑Drp1 or ↓Opa1/Marf)** 2. **Driving fusion (↑Opa1 ± Marf or ↓Drp1)** Crucially, **these effects are cell‑type specific** —the same manipulations in projection neurons or Kenyon cells do **not** alter sleep—which pinpoints dFBN mitochondrial form as a direct lever on sleep homeostasis rather than a general neurodevelopmental or toxicity artifact. ([Nature](https://www.nature.com/articles/s41586-025-09261-y "Mitochondrial origins of the pressure to sleep | Nature")) * * * ### Does calorie restriction promote mitochondrial fusion / Opa1 up‑regulation? The answer is: **it depends on tissue and context**. - In **mouse hepatocytes** subjected to 40 % caloric restriction for 6 months, **Drp1 and Fis1 (fission markers) actually increased**, whereas the core fusion proteins **Mfn1, Mfn2 and Opa1 showed no change**. ([PubMed](https://pubmed.ncbi.nlm.nih.gov/23403066/?utm_source=chatgpt.com "Alterations of Ultrastructural and fission/fusion Markers in ... - PubMed")) - By contrast, in **rodent skeletal muscle** CR **combined with resistance training** led to **elevated levels of Opa1 and Mfn1** , linking fusion machinery up‑regulation to improved muscle mitochondrial function under energy limitation plus demand. ([Physiology Journals](https://journals.physiology.org/doi/10.1152/japplphysiol.00465.2016?utm_source=chatgpt.com "Combined effects of resistance training and calorie restriction on ...")) - More broadly, CR often **enhances mitochondrial biogenesis and coupling efficiency** (via PGC‑1α, SIRT3, etc.), but its direct effects on the balance of fission versus fusion proteins are **tissue‑ and stimulus‑specific** —fusion is not a universal signature of CR in every cell type. * * * **Take‑home** - In sleep‑control neurons, tipping mitochondrial shape toward fission or fusion has **opposite, predictable effects** on sleep and neuronal excitability. - **Calorie restriction** does remodel mitochondrial networks, but it doesn’t uniformly up‑regulate Opa1 across all tissues— **some cells** (e.g., muscle under load) boost fusion proteins, while **others** (e.g., liver) may actually lean toward fission or show no change in Opa1. Overexpressing **Drp1** vs. **Opa1** has very different—and almost opposite—effects on mitochondrial form and cell health: 1. **Drp1 overexpression (“forced fission”)** 2. **Opa1 overexpression (“forced fusion”)** * * * **Bottom line:** Overexpressing **Drp1** (fission) is far more deleterious—raising ROS, collapsing ATP synthesis and triggering cell death—whereas overexpressing **Opa1** (fusion) generally enhances mitochondrial function, lowers oxidative stress and promotes cell survival. ==== Calorie restriction does engage the fission machinery—but **not** as a simple, uniform “↑Drp1 = ↑fission” across every tissue or age. Instead, CR appears to **dynamically modulate** mitochondrial shape to first **prime fission‑mediated clearance** of damaged organelles and then favor **fusion‑driven network integrity**. 1. **CR‑driven fission for mitophagy** 2. **CR‑dependent anti‑aging “fine‑tuning”** 3. **Context matters** * * * **Bottom line:** CR doesn’t simply crank up Drp1 everywhere. Rather, it **orchestrates a “fission pulse”** when damaged mitochondria need clearing (often via Drp1‐dependent cardiolipin signalling), then **rebalances toward fusion** (Opa1/Mfn2) to rebuild a healthy network. Which effect predominates depends on **tissue type, age, and metabolic state**. ---
**Author:** ![AlexKChen](https://www.rapamycin.news/user_avatar/www.rapamycin.news/alexkchen/32/385_2.png) [@AlexKChen](https://www.rapamycin.news/u/AlexKChen)\ **Post date:** [July 22, 2025, 7:41pm UTC](https://www.rapamycin.news/t/is-mitochondrial-fragmentation-drp1-more-likely-to-be-good-than-mitochondrial-fusion-opa1-does-damaging-mitochondria-to-an-extent-increase-selection-pressure/13535/6 "2025-07-22T19:41:26Z")
**Drp1 sensitizes mitochondria to MPT, whereas Opa1 protects against it.** * * * ### Drp1 and increased MPT sensitivity - **Drp1 translocation to mitochondria** promotes excessive mPTP opening by directly interacting with pore components (BAX, PiC) and inactivating protective factors like HK2 after hypoxia [PubMed](https://pubmed.ncbi.nlm.nih.gov/34741026/?utm_source=chatgpt.com). - **Overexpression of Drp1** in permeabilized cells lowers the mitochondrial calcium‑retention capacity (mCRC)—a classic assay for MPT sensitivity—so that lower Ca²⁺ loads trigger pore opening [ResearchGate](https://www.researchgate.net/figure/Drp1-sensitizes-mitochondria-to-calcium-induced-permeability-transition-A-Ca-2_fig2_7733578?utm_source=chatgpt.com). ### Opa1 and resistance to MPT - **Opa1 overexpression** (particularly the short S‑OPA1 splice form) tightens cristae and reduces ROS, raising the threshold for Ca²⁺‑ or ROS‑induced MPT [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7212625/?utm_source=chatgpt.com). - **Opa1 knockout in liver** paradoxically induces mitohormesis but nonetheless **decreases sensitivity to drug‑ or Ca²⁺‑triggered MPT** , protecting against liver injury [Nature](https://www.nature.com/articles/s41467-023-42564-0?utm_source=chatgpt.com). * * * #### Bottom line - **Driving fission** via Drp1 makes mitochondria more prone to permeability‑transition pore opening (lower Ca²⁺ thresholds, higher ROS–driven pore tips). - **Driving fusion** via Opa1 does the opposite—stabilizing cristae, reducing electron leak, and **raising** the resistance of the inner membrane to MPT.