Mitochondria
December 15, 2025, 11:49 AM
Advances in mitochondrial disease knowledge 2025
The field of mitochondrial disease research is rapidly evolving, with significant advancements expected in 2025. Here are some of the key developments anticipated:
These advancements are set to redefine the treatment landscape for mitochondrial diseases, offering new hope for patients and paving the way for future research and therapies.
Mitochondria are intracellular organelles found in almost all human cells. They are responsible for aerobic metabolism through oxidative phosphorylation, which leads to energy production in the form of adenosine triphosphate (ATP).
Mitochondria are thought to be derived from aerobic bacteria that invaded the proto eukaryotic cell more than a billion years ago and lived in a symbiotic relationship with it, exchanging energy in the form of ATP for residence. However, this "endosymbiotic hypothesis" is not universally accepted and has been challenged.
Each human cell contains on average hundreds to thousands of mitochondria. The exception is mature red blood cells, which rely exclusively on anaerobic metabolism and contain no mitochondria.
The respiratory chain is composed of four multi-subunit complexes (I, II, III, and IV) linked by the mobile electron carriers coenzyme Q and cytochrome c. The reduced forms of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) are formed from the citric acid cycle and the beta-oxidation of fatty acids in the mitochondrial matrix. The respiratory chain transfers electrons from NADH (via complex I) and from reduced flavoproteins (via complex II and electron transfer flavoprotein-coenzyme Q oxidoreductase [ETF-Qo]) to coenzyme Q, then complex III, cytochrome c and finally complex IV. At the same time, complexes I, III, and IV pump electrons across the inner mitochondrial membrane from the matrix to the intermembrane space. The influx of these electrons (protons) back into the mitochondrial matrix releases energy that is used in the phosphorylation of ADP to ATP by complex V (ATP synthetase), which is also embedded in the inner mitochondrial membrane..
Mitochondriaare known as the powerhouses of the cell. They are organelles that act like a digestive system which takes in nutrients, breaks them down, and creates energy rich molecules for the cell. The biochemical processes of the cell are known as cellular respiration. Many of the reactions involved in cellular respiration happen in the mitochondria. Mitochondria are the working organelles that keep the cell full of energy.
Mitochondria are small organelles floating free throughout the cell. Some cells have several thousand mitochondria while others have none. Muscle cells need a lot of energy so they have loads of mitochondria. Neurons (cells that transmit nerve impulses) don’t need as many. If a cell feels it is not getting enough energy to survive, more mitochondria can be created. Sometimes a mitochondria can grow larger or combine with other mitochondria. It all depends on the needs of the cell.
Map of the human mitochondrial DNA genome (16569 bp, NCBI sequence accession NC_012920).
Emmanuel Douzery. Picture.
The H (heavy, outer circle) and L (light, inner circle) strands are given with their corresponding genes. There are 22 transfer RNA (TRN) genes for the following amino acids: F, V, L1 (codon UUA/G), I, Q, M, W, A, N, C, Y, S1 (UCN), D, K, G, R, H, S2 (AGC/U), L2 (CUN), E, T and P (white boxes). There are 2 ribosomal RNA (RRN) genes: S (small subunit, or 12S) and L (large subunit, or 16S) (blue boxes). There are 13 protein-coding genes: 7 for NADH dehydrogenase subunits (ND, yellow boxes), 3 for cytochrome c oxidase subunits (COX, orange boxes), 2 for ATPase subunits (ATP, red boxes), and one for cytochrome b (CYTB, coral box). Two gene overlaps are indicated (ATP8-ATP6, and ND4L-ND4, black boxes).
The control region (CR) is the longest non-coding sequence (grey box). Its three hyper-variable regions are indicated (HV, green boxes).
An individual's mitochondrial genes are not inheritedby the same mechanism as nuclear genes. Typically, the mitochondria are inherited from one parent only. In humans, when an egg cell is fertilized by a sperm, the egg nucleus and sperm nucleus each contribute equally to the genetic makeup of the zygote nucleus. In contrast, the mitochondria, and therefore the mitochondrial DNA, usually come from the egg only. The sperm's mitochondria enter the egg, but do not contribute genetic information to the embryo. Instead, paternal mitochondria are marked with ubiquitin to select them for later destruction inside the embryo. The egg cell contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. Mitochondria are, therefore, in most cases inherited only from mothers, a pattern known as maternal inheritance. This mode is seen in most organisms, including the majority of animals.
Despite decades of research, mitochondrial epigenetics remains a controversial notion. Recent findings, however, indicate that dysfunctional mitochondrial DNA (mtDNA) methylation could underlie aging and disease. Unraveling such a level of regulation will be essential in the understanding of and in interfering with the role of mitochondria in many physiological and pathophysiological processes. See reference on mitochondria and epigenetics opposite. So if the mitondrial DNA is altered by epigenetic changes then the inheritance is the same as any mitochondrial DNA is inherited i.e. maternal.
Quora explanation.
Ok, so nuclear DNA and mitochondrial DNA are different in a lot of ways, but the quickest way to show just how different is to show some pictures. Don’t worry, I’ll go into all the boring little details too. There is no way I wouldn’t when it comes to this subject, but pictures first. Normal human genome first.
This is your mitochondrial genome, the whole thing.
So, pretty different right? The nuclear genome is this huge compilation of lots of DNA split up into chromosomes. It isn’t really split up like this in the nucleus but showing it this way gives you a visual as to how much information there is in there. The mitochondrial genome is just one little circle of DNA. As has been mentioned already, there is one other type of organism on earth that has circular genomes, bacteria.
The mitochondria almost certainly evolved from bacteria.There is simply no better explanation for the weirdness of their genomes than this. I don’t just mean the fact that they are circular either. When you delve into what the genes on the mitochondrial genome actually do, it becomes even more apparent that this thing wasn’t originally part of our cells. This was once a parasite, a bacteria that infected some pre-eukaryotic cell billions of years ago, and eventually evolved into an integral part of its host. Mitochondria produce ATP (energy) in far greater quantities than can be made in the cytosol of the cell. In fact, the mitochondria can produce ATP up to 19 times faster than the cytosol. This means that when this first proto-eukaryotic cell picked up its bacterial passenger, it suddenly had access to 16 to 19 times more energy than it did before. It isn’t hard to see how this cell outcompeted its neighbors. So, I just asserted this crazy thing, that the mitochondria are bacterial parasites that have evolved to live inside our cells. I even said that this was obvious when you looked at the genome, but obviously I can’t just leave it there. I only asserted these things. If you are to accept such a crazy hypothesis, of course you need to see the evidence. We have already seen that the mitochondrial DNA is circular. Now lets look at the functions of the genes. Don’t worry. This is a small genome. It only has 37 genes and I won’t need to discuss every one individually. You’ll see why in a moment.
13 of the genes on the mitochondrial genome produce parts for the electron transport chain. This is the structure that produces all that energy that makes the mitochondria so valuable. Ok, no surprises there, but what about the other 24 genes? This is where it gets interesting.
See, one other major difference between bacteria and eukaryotes, besides the structure of their DNA, is how they translate their genetic instructions into proteins. All organisms produce proteins in essentially the same way. The instructions for the protein are encoded in the DNA. An mRNA transcript is made from the DNA sequence for a particular protein, that mRNA then leaves the nucleus, where this coded information is translated into a protein by linking amino acids together in a sequence specified by the code. This last step is facilitated through the help of two other kinds of RNA, tRNA and rRNA. rRNA is what the ribosomes are made of. The ribosomes are the “factories” that actually make the proteins. tRNAs collect amino acids from the cytosol, bring them to the ribosome, and then line them up in accordance with the RNA code. Every tRNA associates a particular amino acid with a particular 3 letter RNA sequence, called a codon. For instance, the letters AUG code for the amino acid methionine, so the tRNA that picks up methionine will always bond to the letters AUG on the mRNA.
Well, the “code” is slightly different between eukaryotes and bacteria. All of our letters don’t always code for all of the the same amino acids. Our tRNAs basically read different languages. Our ribosomes are also structured a little different. RNA transcripts in eukaryotic cells are packaged in a very specific way to facilitate their binding correctly to the ribosome, and bacteria don’t package their RNA in quite the same way that we do so their ribosomes aren’t built the same way either. By now you may have guessed what the rest of the genes on the mitochondrial genome do, they code for tRNAs and rRNAs. The mitochondria can’t use ours because they are basically speaking a different language from our cells. The cell is running windows and the mitochondria are running mac. Because of this, they have to make all of their own translation machinery. More of the mitochondrial genome is used for making translation machinery so that it can make proteins than is actually used to make proteins. And all of the differences between mitochondrial translation machinery and the machinery used in the rest of the cell are consistent with the differences seen between eukaryotes and bacteria.
So mitochondria have weird, suspiciously bacterial-looking genomes that mostly code for weird, suspiciously bacterial-looking protein translation machinery. There are also some oddities with their membrane structure but that isn’t related to the genome so I won’t touch on it here. You know what they say though, if it walks like a bacterium and talks like a bacterium… This is why we are pretty confident in our crazy hypothesis, and why the mitochondrial genome is evidence of just how weird our own evolutionary history can be.
P.S: MT-RNR2, which codes for the lower subunit of the ribosome, also codes for a protein called humanin that helps regulate programmed cell death. This is also an odd, bacterial-looking trait, but I couldn’t think of where to put it so I’m just tagging it in at the bottom. Bacteria have all sorts of clever tricks for encoding more than one protein on the same gene to save space in their limited genomes. Eukaryotes have giant genomes full of so much DNA that they don’t even use it all. For this reason, we don’t tend to do this…except here. Coincidence?