**Core Concept**
Apoptosis, also known as programmed cell death, is a vital cellular process that eliminates damaged or unwanted cells from the body. It involves a series of morphological and biochemical changes that ultimately lead to the death of the cell.

**Why the Correct Answer is Right**
The earliest change seen in apoptosis is the loss of mitochondrial membrane potential, which is mediated by the release of cytochrome c from the mitochondria into the cytosol. This event triggers the formation of the apoptosome, a multiprotein complex that activates caspase-9, a key enzyme in the caspase cascade. The loss of mitochondrial membrane potential is a critical step in the initiation of apoptosis.

**Why Each Wrong Option is Incorrect**
**Option A:** DNA fragmentation is a later event in apoptosis, occurring after the activation of caspases and the breakdown of the nuclear membrane.
**Option B:** Endoplasmic reticulum stress is a stimulus for apoptosis, but it is not an early change seen in the process.
**Option C:** Phosphatidylserine externalization is a feature of late-stage apoptosis, occurring after the cell has undergone significant morphological changes.

**Clinical Pearl / High-Yield Fact**
It's essential to remember that the loss of mitochondrial membrane potential is a key early event in apoptosis, and its disruption can lead to a range of cellular abnormalities and diseases, including neurodegenerative disorders and cancer.

**Correct Answer: C. Phosphatidylserine externalization is a feature of late-stage apoptosis, occurring after the cell has undergone significant morphological changes.**